NM_206933.4:c.6326-19094A>T

Variant names:

• chr1-216019656-T-A
• rs6540927
• NM_206933.4:c.6326-19094A>T

Variant summary

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

The NM_206933.4(USH2A):​c.6326-19094A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,074 control chromosomes in the GnomAD database, including 28,893 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 0.61 (28893 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH2A	NM_206933.4	c.6326-19094A>T		intron_variant	Intron 32 of 71	ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.6326-19094A>T		intron_variant	Intron 32 of 71	1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083.1	c.6326-19094A>T		intron_variant	Intron 32 of 72			ENSP00000501296.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93119 AN: 151954 Hom.: 28884 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.613 AC: 93170 AN: 152074 Hom.: 28893 Cov.: 32 AF XY: 0.618 AC XY: 45910 AN XY: 74344

African (AFR) AF: 0.544 AC: 22559 AN: 41468

American (AMR) AF: 0.660 AC: 10092 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2225 AN: 3468

East Asian (EAS) AF: 0.752 AC: 3882 AN: 5162

South Asian (SAS) AF: 0.555 AC: 2677 AN: 4824

European-Finnish (FIN) AF: 0.717 AC: 7591 AN: 10582

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41926 AN: 67970

Other (OTH) AF: 0.633 AC: 1337 AN: 2112

Alfa AF: 0.621 Hom.: 3654

Bravo AF: 0.614

Asia WGS AF: 0.620 AC: 2153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.32
PhyloP100		-0.67
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: rs6540927; hg19: chr1-216192998;