1-215714587-T-G

Position:

• chr1-215714587-T-G

Variant summary

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

The NM_206933.4(USH2A):​c.12066+13443A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,082 control chromosomes in the GnomAD database, including 12,857 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 0.40 (12857 hom., cov: 33)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH2A	NM_206933.4	c.12066+13443A>C		intron_variant		ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.12066+13443A>C		intron_variant		1	NM_206933.4	ENSP00000305941	P1
USH2A	ENST00000674083.1	c.12066+13443A>C		intron_variant				ENSP00000501296

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60710 AN: 151964 Hom.: 12837 Cov.: 33

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.400 AC: 60765 AN: 152082 Hom.: 12857 Cov.: 33 AF XY: 0.397 AC XY: 29495 AN XY: 74342

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.399

Alfa AF: 0.341 Hom.: 11711

Bravo AF: 0.411

Asia WGS AF: 0.384 AC: 1333 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.68

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: rs6656554; hg19: chr1-215887929; COSMIC: COSV56344474;