1-215625732-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_206933.4(USH2A):c.*49A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,549,140 control chromosomes in the GnomAD database, including 706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (203 hom., cov: 32)
  • Exomes 𝑓: 0.013 (503 hom.)
• Consequence: USH2A NM_206933.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.148

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-215625732-T-G is Benign according to our data. Variant chr1-215625732-T-G is described in ClinVar as [Benign]. Clinvar id is 1227419.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-215625732-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.*49A>C		3_prime_UTR_variant	72/72	ENST00000307340.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.*49A>C		3_prime_UTR_variant	72/72	1	NM_206933.4	P1
USH2A	ENST00000674083.1	c.*49A>C		3_prime_UTR_variant	73/73

Frequencies

GnomAD3 genomes AF: 0.0330 AC: 5022 AN: 152106 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0287

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00409

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0199 AC: 4983 AN: 250738 Hom.: 166 AF XY: 0.0209 AC XY: 2829 AN XY: 135518

Gnomad AFR exome AF: 0.0926

Gnomad AMR exome AF: 0.00786

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.0187

Gnomad SAS exome AF: 0.0712

Gnomad FIN exome AF: 0.00301

Gnomad NFE exome AF: 0.00461

Gnomad OTH exome AF: 0.0133

GnomAD4 exome AF: 0.0126 AC: 17660 AN: 1396916 Hom.: 503 Cov.: 23 AF XY: 0.0140 AC XY: 9759 AN XY: 698764

Gnomad4 AFR exome AF: 0.0958

Gnomad4 AMR exome AF: 0.00870

Gnomad4 ASJ exome AF: 0.00229

Gnomad4 EAS exome AF: 0.0494

Gnomad4 SAS exome AF: 0.0678

Gnomad4 FIN exome AF: 0.00251

Gnomad4 NFE exome AF: 0.00498

Gnomad4 OTH exome AF: 0.0168

GnomAD4 genome AF: 0.0331 AC: 5041 AN: 152224 Hom.: 203 Cov.: 32 AF XY: 0.0325 AC XY: 2418 AN XY: 74432

Gnomad4 AFR AF: 0.0937

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0290

Gnomad4 SAS AF: 0.0710

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.00409

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.00991 Hom.: 34

Bravo AF: 0.0343

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.37
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7531580; hg19: chr1-215799074;