chr1-215819066-A-G

Variant names:

• chr1-215819066-A-G
• rs10495006
• NM_206933.4:c.9372-1871T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206933.4(USH2A):​c.9372-1871T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 151,990 control chromosomes in the GnomAD database, including 169 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 0.036 (169 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701
• Publications: 2 publications found

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]

USH2A Gene-Disease associations (from GenCC):

• Usher syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 39

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4	c.9372-1871T>C		intron_variant	Intron 47 of 71	ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.9372-1871T>C		intron_variant	Intron 47 of 71	1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083.1	c.9372-1871T>C		intron_variant	Intron 47 of 72			ENSP00000501296.1

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5467 AN: 151872 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.00660

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0359 AC: 5464 AN: 151990 Hom.: 169 Cov.: 32 AF XY: 0.0364 AC XY: 2703 AN XY: 74284

African (AFR) AF: 0.0102 AC: 423 AN: 41570

American (AMR) AF: 0.0535 AC: 814 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.152 AC: 784 AN: 5170

South Asian (SAS) AF: 0.0766 AC: 370 AN: 4828

European-Finnish (FIN) AF: 0.00660 AC: 70 AN: 10612

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0420 AC: 2845 AN: 67812

Other (OTH) AF: 0.0469 AC: 99 AN: 2110

Alfa AF: 0.0324 Hom.: 18

Bravo AF: 0.0369

Asia WGS AF: 0.119 AC: 412 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.65
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10495006; hg19: chr1-215992408;