rs1544299

Variant names:

• chr1-216091046-A-C
• rs1544299
• NM_206933.4:c.4759-1907T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-216091046-A-C
• chr1-216091046-A-G

Variant summary

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

The NM_206933.4(USH2A):​c.4759-1907T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,958 control chromosomes in the GnomAD database, including 11,577 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 0.38 (11577 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4	c.4759-1907T>G		intron_variant	Intron 22 of 71	ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.4759-1907T>G		intron_variant	Intron 22 of 71	1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083.1	c.4759-1907T>G		intron_variant	Intron 22 of 72			ENSP00000501296.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57084 AN: 151840 Hom.: 11570 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.376 AC: 57112 AN: 151958 Hom.: 11577 Cov.: 32 AF XY: 0.384 AC XY: 28507 AN XY: 74254

African (AFR) AF: 0.307 AC: 12724 AN: 41460

American (AMR) AF: 0.488 AC: 7449 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1435 AN: 3468

East Asian (EAS) AF: 0.848 AC: 4370 AN: 5154

South Asian (SAS) AF: 0.488 AC: 2347 AN: 4814

European-Finnish (FIN) AF: 0.396 AC: 4185 AN: 10558

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.344 AC: 23370 AN: 67928

Other (OTH) AF: 0.399 AC: 840 AN: 2106

Alfa AF: 0.362 Hom.: 29857

Bravo AF: 0.384

Asia WGS AF: 0.610 AC: 2123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.96
DANN	Benign	0.74
PhyloP100		0.24
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: rs1544299; hg19: chr1-216264388; COSMIC: COSV56345862; COSMIC: COSV56345862;