chr1-216330927-A-G

Variant names:

• chr1-216330927-A-G
• rs7532570
• NM_206933.4:c.785-3273T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_206933.4(USH2A):​c.785-3273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 152,134 control chromosomes in the GnomAD database, including 294 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 0.053 (294 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206933.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	NM_206933.4	MANE Select	c.785-3273T>C		intron	N/A	NP_996816.3
	USH2A	NM_007123.6		c.785-3273T>C		intron	N/A	NP_009054.6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	ENST00000307340.8	TSL:1 MANE Select	c.785-3273T>C		intron	N/A	ENSP00000305941.3
	USH2A	ENST00000366942.3	TSL:1	c.785-3273T>C		intron	N/A	ENSP00000355909.3
	USH2A	ENST00000674083.1		c.785-3273T>C		intron	N/A	ENSP00000501296.1

Frequencies

GnomAD3 genomes AF: 0.0529 AC: 8041 AN: 152016 Hom.: 293 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0774

Gnomad OTH AF: 0.0613

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

GnomAD4 genome AF: 0.0529 AC: 8047 AN: 152134 Hom.: 294 Cov.: 32 AF XY: 0.0518 AC XY: 3853 AN XY: 74386

African (AFR) AF: 0.0154 AC: 640 AN: 41534

American (AMR) AF: 0.0478 AC: 729 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 340 AN: 3472

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5172

South Asian (SAS) AF: 0.0712 AC: 343 AN: 4818

European-Finnish (FIN) AF: 0.0470 AC: 499 AN: 10610

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0774 AC: 5260 AN: 67966

Other (OTH) AF: 0.0635 AC: 134 AN: 2110

Alfa AF: 0.0565 Hom.: 244

Bravo AF: 0.0505

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		0.33
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: rs7532570; hg19: chr1-216504269;