rs2034960

Positions:

• chr1-216185060-G-A
• chr1-216185060-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000307340.8(USH2A):​c.4396+5163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,628 control chromosomes in the GnomAD database, including 25,479 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (25479 hom., cov: 32)
• Consequence: USH2A ENST00000307340.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961

Genes affected

USH2A (HGNC:12601): (usherin) This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH2A	NM_206933.4	c.4396+5163C>T		intron_variant		ENST00000307340.8	NP_996816.3
USH2A	NM_007123.6	c.4396+5163C>T		intron_variant			NP_009054.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.4396+5163C>T		intron_variant		1	NM_206933.4	ENSP00000305941	P1
USH2A	ENST00000366942.3	c.4396+5163C>T		intron_variant		1		ENSP00000355909
USH2A	ENST00000674083.1	c.4396+5163C>T		intron_variant				ENSP00000501296

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85464 AN: 151510 Hom.: 25467 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.564 AC: 85496 AN: 151628 Hom.: 25479 Cov.: 32 AF XY: 0.573 AC XY: 42416 AN XY: 74046

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.575

Alfa AF: 0.587 Hom.: 3384

Bravo AF: 0.550

Asia WGS AF: 0.692 AC: 2406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.46

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: rs2034960; hg19: chr1-216358402; COSMIC: COSV56346112;