1-216378749-C-T

Position:

• chr1-216378749-C-T

Variant summary

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

The NM_206933.4(USH2A):​c.652-13664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,834 control chromosomes in the GnomAD database, including 26,675 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 0.58 (26675 hom., cov: 31)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH2A	NM_206933.4	c.652-13664G>A		intron_variant		ENST00000307340.8	NP_996816.3
USH2A	NM_007123.6	c.652-13664G>A		intron_variant			NP_009054.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.652-13664G>A		intron_variant		1	NM_206933.4	ENSP00000305941	P1
USH2A	ENST00000366942.3	c.652-13664G>A		intron_variant		1		ENSP00000355909
USH2A	ENST00000674083.1	c.652-13664G>A		intron_variant				ENSP00000501296

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87578 AN: 151716 Hom.: 26657 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.577 AC: 87623 AN: 151834 Hom.: 26675 Cov.: 31 AF XY: 0.582 AC XY: 43213 AN XY: 74192

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.588

Alfa AF: 0.629 Hom.: 47258

Bravo AF: 0.564

Asia WGS AF: 0.661 AC: 2297 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.61

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: rs2669053; hg19: chr1-216552091;