rs41304083

Variant names:

• chr1-215648629-G-A
• rs41304083
• NM_206933.4:c.14481C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-215648629-G-A
• chr1-215648629-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_206933.4(USH2A):​c.14481C>T​(p.Ala4827Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,614,160 control chromosomes in the GnomAD database, including 517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (100 hom., cov: 33)
  • Exomes 𝑓: 0.011 (417 hom.)
• Consequence: USH2A NM_206933.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.310
• Publications: 6 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 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Usher syndrome type 2

  Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-215648629-G-A is Benign according to our data. Variant chr1-215648629-G-A is described in ClinVar as Benign. ClinVar VariationId is 48438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.064 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.14481C>T	p.Ala4827Ala	synonymous	Exon 66 of 72	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.14481C>T	p.Ala4827Ala	synonymous	Exon 66 of 72	ENSP00000305941.3	O75445-1
	USH2A	ENST00000674083.1		c.14481C>T	p.Ala4827Ala	synonymous	Exon 66 of 73	ENSP00000501296.1	O75445-3

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3539 AN: 152188 Hom.: 97 Cov.: 33

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00354

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.0168 AC: 4218 AN: 251396 AF XY: 0.0183

Gnomad AFR exome AF: 0.0644

Gnomad AMR exome AF: 0.00396

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0188

Gnomad FIN exome AF: 0.00300

Gnomad NFE exome AF: 0.00388

Gnomad OTH exome AF: 0.00994

GnomAD4 exome AF: 0.0109 AC: 15977 AN: 1461854 Hom.: 417 Cov.: 31 AF XY: 0.0122 AC XY: 8897 AN XY: 727224

African (AFR) AF: 0.0658 AC: 2202 AN: 33476

American (AMR) AF: 0.00467 AC: 209 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.0506 AC: 2008 AN: 39700

South Asian (SAS) AF: 0.0665 AC: 5739 AN: 86250

European-Finnish (FIN) AF: 0.00253 AC: 135 AN: 53418

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5768

European-Non Finnish (NFE) AF: 0.00435 AC: 4839 AN: 1111990

Other (OTH) AF: 0.0131 AC: 793 AN: 60392

GnomAD4 genome AF: 0.0233 AC: 3552 AN: 152306 Hom.: 100 Cov.: 33 AF XY: 0.0238 AC XY: 1773 AN XY: 74458

African (AFR) AF: 0.0620 AC: 2578 AN: 41574

American (AMR) AF: 0.0103 AC: 158 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.0300 AC: 155 AN: 5168

South Asian (SAS) AF: 0.0702 AC: 338 AN: 4818

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00354 AC: 241 AN: 68032

Other (OTH) AF: 0.0156 AC: 33 AN: 2116

Alfa AF: 0.0114 Hom.: 26

Bravo AF: 0.0235

Asia WGS AF: 0.0530 AC: 186 AN: 3478

EpiCase AF: 0.00447

EpiControl AF: 0.00320

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Usher syndrome type 2A (2)
-	-	1	Retinal dystrophy (1)
-	-	1	Retinitis pigmentosa 39 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.58
DANN	Benign	0.61
PhyloP100		0.31
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41304083; hg19: chr1-215821971;