chr1-215941896-C-T

Position:

• chr1-215941896-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_206933.4(USH2A):​c.7121-7101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 152,240 control chromosomes in the GnomAD database, including 91 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 0.028 (91 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0284 (4327/152240) while in subpopulation NFE AF= 0.0415 (2822/68012). AF 95% confidence interval is 0.0402. There are 91 homozygotes in gnomad4. There are 2139 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 91 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.7121-7101G>A		intron_variant		ENST00000307340.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.7121-7101G>A		intron_variant		1	NM_206933.4	P1
USH2A	ENST00000674083.1	c.7121-7101G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4329 AN: 152124 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.00676

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00457

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0267

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

GnomAD4 genome AF: 0.0284 AC: 4327 AN: 152240 Hom.: 91 Cov.: 32 AF XY: 0.0287 AC XY: 2139 AN XY: 74416

Gnomad4 AFR AF: 0.00674

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00457

Gnomad4 FIN AF: 0.0583

Gnomad4 NFE AF: 0.0415

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0376 Hom.: 39

Bravo AF: 0.0245

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.70

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: rs17581848; hg19: chr1-216115238;