rs62093482

Positions:

• chr18-31598936-C-T

Variant summary

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

The XR_007066326.1(LOC124904277):​n.129-3241G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 508,938 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (34 hom., cov: 33)
  • Exomes 𝑓: 0.024 (124 hom.)
• Consequence: LOC124904277 XR_007066326.1 intron, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.482

Genes affected

LOC124904277 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 18-31598936-C-T is Benign according to our data. Variant chr18-31598936-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 892146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0183 (2785/152192) while in subpopulation NFE AF= 0.0285 (1939/68014). AF 95% confidence interval is 0.0275. There are 34 homozygotes in gnomad4. There are 1320 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904277	XR_007066326.1	n.129-3241G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2788 AN: 152074 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00527

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0237 AC: 8455 AN: 356746 Hom.: 124 Cov.: 3 AF XY: 0.0232 AC XY: 4400 AN XY: 189844

Gnomad4 AFR exome AF: 0.00590

Gnomad4 AMR exome AF: 0.0116

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.000543

Gnomad4 SAS exome AF: 0.0212

Gnomad4 FIN exome AF: 0.0221

Gnomad4 NFE exome AF: 0.0293

Gnomad4 OTH exome AF: 0.0217

GnomAD4 genome AF: 0.0183 AC: 2785 AN: 152192 Hom.: 34 Cov.: 33 AF XY: 0.0177 AC XY: 1320 AN XY: 74414

Gnomad4 AFR AF: 0.00525

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.0255 Hom.: 46

Bravo AF: 0.0169

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Amyloidosis, hereditary systemic 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.7
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs62093482; hg19: chr18-29178899;