1-216258898-A-G

Position:

• chr1-216258898-A-G

Variant summary

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

The NM_206933.4(USH2A):​c.1972-7800T>C 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 151,872 control chromosomes in the GnomAD database, including 26,954 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 (26954 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.1972-7800T>C		intron_variant		ENST00000307340.8
USH2A	NM_007123.6	c.1972-7800T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.1972-7800T>C		intron_variant		1	NM_206933.4	P1
USH2A	ENST00000366942.3	c.1972-7800T>C		intron_variant		1
USH2A	ENST00000674083.1	c.1972-7800T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87520 AN: 151754 Hom.: 26941 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.577 AC: 87556 AN: 151872 Hom.: 26954 Cov.: 32 AF XY: 0.585 AC XY: 43425 AN XY: 74262

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.600

Alfa AF: 0.607 Hom.: 4844

Bravo AF: 0.560

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.72

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: rs10864235; hg19: chr1-216432240;