rs1544299

chr1-216091046-A-Cchr1-216091046-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.4759-1907T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,958 control chromosomes in the GnomAD database, including 11,577 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 0.38 (11577 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.4759-1907T>G		intron_variant		ENST00000307340.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.4759-1907T>G		intron_variant		1	NM_206933.4	P1
USH2A	ENST00000674083.1	c.4759-1907T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57084 AN: 151840 Hom.: 11570 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.376 AC: 57112 AN: 151958 Hom.: 11577 Cov.: 32 AF XY: 0.384 AC XY: 28507 AN XY: 74254

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.399

Alfa AF: 0.365 Hom.: 18492

Bravo AF: 0.384

Asia WGS AF: 0.610 AC: 2123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.96
Dann	Benign	0.74

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: rs1544299; hg19: chr1-216264388; COSMIC: COSV56345862; COSMIC: COSV56345862;