rs4330896

Positions:

• chr1-215731531-G-A
• chr1-215731531-G-C

Variant summary

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

The NM_206933.4(USH2A):​c.11712-3147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,030 control chromosomes in the GnomAD database, including 36,206 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 0.68 (36206 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH2A	NM_206933.4	c.11712-3147C>T		intron_variant		ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.11712-3147C>T		intron_variant		1	NM_206933.4	ENSP00000305941	P1
USH2A	ENST00000674083.1	c.11712-3147C>T		intron_variant				ENSP00000501296

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103323 AN: 151912 Hom.: 36195 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.680 AC: 103352 AN: 152030 Hom.: 36206 Cov.: 32 AF XY: 0.675 AC XY: 50177 AN XY: 74304

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.696

Alfa AF: 0.755 Hom.: 23256

Bravo AF: 0.666

Asia WGS AF: 0.608 AC: 2114 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.26

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: rs4330896; hg19: chr1-215904873;