1-215625538-C-A

Position:

• chr1-215625538-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_206933.4(USH2A):​c.*243G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0085 in 543,290 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (105 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (34 hom.)
• Consequence: USH2A NM_206933.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.335

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-215625538-C-A is Benign according to our data. Variant chr1-215625538-C-A is described in ClinVar as [Benign]. Clinvar id is 1297792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH2A	NM_206933.4	c.*243G>T		3_prime_UTR_variant	72/72	ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340	c.*243G>T		3_prime_UTR_variant	72/72	1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083	c.*243G>T		3_prime_UTR_variant	73/73			ENSP00000501296.1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3292 AN: 152112 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.00338 AC: 1323 AN: 391060 Hom.: 34 Cov.: 3 AF XY: 0.00283 AC XY: 589 AN XY: 208236

Gnomad4 AFR exome AF: 0.0725

Gnomad4 AMR exome AF: 0.00622

Gnomad4 ASJ exome AF: 0.00153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000904

Gnomad4 OTH exome AF: 0.00735

GnomAD4 genome AF: 0.0217 AC: 3297 AN: 152230 Hom.: 105 Cov.: 32 AF XY: 0.0197 AC XY: 1464 AN XY: 74432

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0171 Hom.: 11

Bravo AF: 0.0244

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.58

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: rs74400441; hg19: chr1-215798880;