chr1-216084852-G-T

Variant names:

• chr1-216084852-G-T
• rs56110889
• NM_206933.4:c.5013C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_206933.4(USH2A):​c.5013C>A​(p.Gly1671Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,611,682 control chromosomes in the GnomAD database, including 23,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2188 hom., cov: 32)
  • Exomes 𝑓: 0.16 (21000 hom.)
• Consequence: USH2A NM_206933.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.171
• Publications: 14 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-AS2 (HGNC:40605): (USH2A antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 1-216084852-G-T is Benign according to our data. Variant chr1-216084852-G-T is described in ClinVar as Benign. ClinVar VariationId is 48527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.171 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	NM_206933.4	MANE Select	c.5013C>A	p.Gly1671Gly	synonymous	Exon 25 of 72	NP_996816.3	O75445-1
	USH2A-AS2	NR_125992.1		n.266-1870G>T		intron	N/A
	USH2A-AS2	NR_125993.1		n.137-1870G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	ENST00000307340.8	TSL:1 MANE Select	c.5013C>A	p.Gly1671Gly	synonymous	Exon 25 of 72	ENSP00000305941.3	O75445-1
	USH2A	ENST00000674083.1		c.5013C>A	p.Gly1671Gly	synonymous	Exon 25 of 73	ENSP00000501296.1	O75445-3
	USH2A	ENST00000463147.1	TSL:2	n.257C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24671 AN: 151924 Hom.: 2189 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0584

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.133 AC: 33426 AN: 250622 AF XY: 0.133

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.0944

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.163 AC: 237752 AN: 1459640 Hom.: 21000 Cov.: 32 AF XY: 0.161 AC XY: 116997 AN XY: 726212

African (AFR) AF: 0.204 AC: 6826 AN: 33390

American (AMR) AF: 0.0967 AC: 4312 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4379 AN: 26102

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39674

South Asian (SAS) AF: 0.0788 AC: 6800 AN: 86240

European-Finnish (FIN) AF: 0.111 AC: 5912 AN: 53326

Middle Eastern (MID) AF: 0.130 AC: 750 AN: 5754

European-Non Finnish (NFE) AF: 0.180 AC: 199469 AN: 1110254

Other (OTH) AF: 0.154 AC: 9290 AN: 60290

GnomAD4 genome AF: 0.162 AC: 24671 AN: 152042 Hom.: 2188 Cov.: 32 AF XY: 0.156 AC XY: 11608 AN XY: 74314

African (AFR) AF: 0.193 AC: 8024 AN: 41468

American (AMR) AF: 0.135 AC: 2059 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5166

South Asian (SAS) AF: 0.0576 AC: 278 AN: 4828

European-Finnish (FIN) AF: 0.102 AC: 1073 AN: 10566

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12228 AN: 67964

Other (OTH) AF: 0.144 AC: 305 AN: 2116

Alfa AF: 0.177 Hom.: 997

Bravo AF: 0.167

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	2	Usher syndrome type 2A (2)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.8
DANN	Benign	0.77
PhyloP100		0.17
Mutation Taster		=99/1	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: rs56110889; hg19: chr1-216258194; COSMIC: COSV56425186;