rs148180760

Variant names:

• chr9-131522040-C-A
• rs148180760
• NM_001077365.2:c.1826-7C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-131522040-C-A
• chr9-131522040-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001077365.2(POMT1):​c.1826-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,613,792 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0078 (7 hom., cov: 33)
  • Exomes 𝑓: 0.011 (140 hom.)
• Consequence: POMT1 NM_001077365.2 splice_region, intron
• Scores: Splicing: ADA: 0.1221
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.352

Genes affected

POMT1 (HGNC:9202): (protein O-mannosyltransferase 1) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS) and limb-girdle muscular dystrophy type 2K (LGMD2K). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

ENSG00000230289 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-131522040-C-A is Benign according to our data. Variant chr9-131522040-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 130010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131522040-C-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00779 (1186/152208) while in subpopulation NFE AF= 0.0124 (842/67972). AF 95% confidence interval is 0.0117. There are 7 homozygotes in gnomad4. There are 556 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.1826-7C>A		splice_region_variant, intron_variant	Intron 18 of 19	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.1826-7C>A		splice_region_variant, intron_variant	Intron 18 of 19	1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes AF: 0.00780 AC: 1186 AN: 152088 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00669

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00696 AC: 1749 AN: 251298 Hom.: 11 AF XY: 0.00657 AC XY: 892 AN XY: 135864

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00337

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00677

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.00798

GnomAD4 exome AF: 0.0112 AC: 16442 AN: 1461584 Hom.: 140 Cov.: 31 AF XY: 0.0107 AC XY: 7806 AN XY: 727118

Gnomad4 AFR exome AF: 0.00179

Gnomad4 AMR exome AF: 0.00295

Gnomad4 ASJ exome AF: 0.00402

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.00650

Gnomad4 NFE exome AF: 0.0137

Gnomad4 OTH exome AF: 0.00954

GnomAD4 genome AF: 0.00779 AC: 1186 AN: 152208 Hom.: 7 Cov.: 33 AF XY: 0.00747 AC XY: 556 AN XY: 74416

Gnomad4 AFR AF: 0.00258

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00669

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00991 Hom.: 5

Bravo AF: 0.00773

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0111

EpiControl AF: 0.00931

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.1892-7C>A in intron 18 of POMT1: This variant is not expected to have clinical significance because it has been identified in 1.4% (124/8600) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs148180760). -

Sep 30, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 15, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:3

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

POMT1: BP4, BS1, BS2 -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 16, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2K Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.8
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs148180760; hg19: chr9-134397427;