rs6689120

Variant names:

• chr1-215970606-T-C
• rs6689120
• NM_206933.4:c.6957+19A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-215970606-T-C
• chr1-215970606-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_206933.4(USH2A):​c.6957+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 1,613,192 control chromosomes in the GnomAD database, including 7,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene USH2A is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.096 (759 hom., cov: 32)
  • Exomes 𝑓: 0.095 (7157 hom.)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.66
• Publications: 8 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, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Usher syndrome type 2A

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Specifications for USH2A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-215970606-T-C is Benign according to our data. Variant chr1-215970606-T-C is described in ClinVar as Benign. ClinVar VariationId is 137896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 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.6957+19A>G		intron	N/A	NP_996816.3	O75445-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	ENST00000307340.8	TSL:1 MANE Select	c.6957+19A>G		intron	N/A	ENSP00000305941.3	O75445-1
	USH2A	ENST00000674083.1		c.6957+19A>G		intron	N/A	ENSP00000501296.1	O75445-3

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14620 AN: 152052 Hom.: 754 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0973

Gnomad OTH AF: 0.0929

GnomAD2 exomes AF: 0.0856 AC: 21454 AN: 250630 AF XY: 0.0854

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.0739

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0673

Gnomad NFE exome AF: 0.0911

Gnomad OTH exome AF: 0.0827

GnomAD4 exome AF: 0.0954 AC: 139450 AN: 1461022 Hom.: 7157 Cov.: 32 AF XY: 0.0953 AC XY: 69262 AN XY: 726820

African (AFR) AF: 0.121 AC: 4029 AN: 33430

American (AMR) AF: 0.107 AC: 4771 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.0725 AC: 1894 AN: 26112

East Asian (EAS) AF: 0.000806 AC: 32 AN: 39682

South Asian (SAS) AF: 0.0931 AC: 8028 AN: 86246

European-Finnish (FIN) AF: 0.0687 AC: 3667 AN: 53384

Middle Eastern (MID) AF: 0.0856 AC: 493 AN: 5760

European-Non Finnish (NFE) AF: 0.0999 AC: 111038 AN: 1111436

Other (OTH) AF: 0.0911 AC: 5498 AN: 60336

GnomAD4 genome AF: 0.0962 AC: 14646 AN: 152170 Hom.: 759 Cov.: 32 AF XY: 0.0955 AC XY: 7107 AN XY: 74390

African (AFR) AF: 0.113 AC: 4712 AN: 41542

American (AMR) AF: 0.106 AC: 1619 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 284 AN: 3470

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5166

South Asian (SAS) AF: 0.0844 AC: 407 AN: 4824

European-Finnish (FIN) AF: 0.0704 AC: 747 AN: 10606

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0973 AC: 6617 AN: 68014

Other (OTH) AF: 0.0919 AC: 194 AN: 2110

Alfa AF: 0.0936 Hom.: 277

Bravo AF: 0.0964

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Usher syndrome type 2A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.60
PhyloP100		1.7
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6689120;

hg19: chr1-216143948;

COSMIC: COSV56329676;