rs12095085

Variant names:

• chr1-215758586-T-A
• rs12095085
• NM_206933.4:c.11389+9A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-215758586-T-A
• chr1-215758586-T-C

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.11389+9A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,609,608 control chromosomes in the GnomAD database, including 13,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1273 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11837 hom.)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.449
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-215758586-T-A is Benign according to our data. Variant chr1-215758586-T-A is described in ClinVar as Benign. ClinVar VariationId is 48372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 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.11389+9A>T		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.11389+9A>T		intron	N/A	ENSP00000305941.3	O75445-1
	USH2A	ENST00000674083.1		c.11389+9A>T		intron	N/A	ENSP00000501296.1	O75445-3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18727 AN: 151992 Hom.: 1271 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0452

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.144

GnomAD2 exomes AF: 0.104 AC: 26024 AN: 250720 AF XY: 0.104

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.0683

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.123 AC: 179171 AN: 1457498 Hom.: 11837 Cov.: 34 AF XY: 0.122 AC XY: 88177 AN XY: 725324

African (AFR) AF: 0.135 AC: 4511 AN: 33396

American (AMR) AF: 0.0699 AC: 3126 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3506 AN: 26110

East Asian (EAS) AF: 0.000177 AC: 7 AN: 39644

South Asian (SAS) AF: 0.0545 AC: 4696 AN: 86182

European-Finnish (FIN) AF: 0.151 AC: 7958 AN: 52692

Middle Eastern (MID) AF: 0.126 AC: 650 AN: 5152

European-Non Finnish (NFE) AF: 0.133 AC: 147313 AN: 1109370

Other (OTH) AF: 0.123 AC: 7404 AN: 60236

GnomAD4 genome AF: 0.123 AC: 18731 AN: 152110 Hom.: 1273 Cov.: 32 AF XY: 0.122 AC XY: 9048 AN XY: 74344

African (AFR) AF: 0.135 AC: 5602 AN: 41490

American (AMR) AF: 0.0987 AC: 1508 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 470 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0450 AC: 217 AN: 4824

European-Finnish (FIN) AF: 0.145 AC: 1539 AN: 10578

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.131 AC: 8930 AN: 67978

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.104 Hom.: 334

Bravo AF: 0.120

Asia WGS AF: 0.0250 AC: 88 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.55
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12095085; hg19: chr1-215931928;