NM_001081.4:c.8755+174T>A

Variant names:

• chr10-16890197-A-T
• rs17343073
• NM_001081.4:c.8755+174T>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001081.4(CUBN):​c.8755+174T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0818 in 152,044 control chromosomes in the GnomAD database, including 563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.082 (563 hom., cov: 31)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.694

Genes affected

CUBN (HGNC:2548): (cubilin) Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubulin is located within the epithelium of intestine and kidney. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-16890197-A-T is Benign according to our data. Variant chr10-16890197-A-T is described in ClinVar as [Benign]. Clinvar id is 1290271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.8755+174T>A		intron_variant	Intron 55 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.4741+174T>A		intron_variant	Intron 29 of 40		XP_011518011.1
CUBN	XM_011519710.3	c.4717+174T>A		intron_variant	Intron 29 of 40		XP_011518012.1
CUBN	XM_011519711.4	c.4597+174T>A		intron_variant	Intron 28 of 39		XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.8755+174T>A		intron_variant	Intron 55 of 66	1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12437 AN: 151926 Hom.: 562 Cov.: 31

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0931

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0818 AC: 12433 AN: 152044 Hom.: 563 Cov.: 31 AF XY: 0.0798 AC XY: 5931 AN XY: 74344

Gnomad4 AFR AF: 0.0441

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0781

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0912

Alfa AF: 0.0935 Hom.: 101

Bravo AF: 0.0787

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 07, 2018

GeneDx

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	-0.93
CADD	Benign	0.18
DANN	Benign	0.43

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: rs17343073; hg19: chr10-16932196;