rs7102149

Variant names:

• chr11-77088177-G-A
• rs7102149
• NM_004055.5:c.165+3126G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77088177-G-A
• chr11-77088177-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004055.5(CAPN5):​c.165+3126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,033,198 control chromosomes in the GnomAD database, including 56,987 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 0.30 (7211 hom., cov: 29)
  • Exomes 𝑓: 0.31 (49776 hom.)
• Consequence: CAPN5 NM_004055.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 2 publications found

Genes affected

CAPN5 (HGNC:1482): (calpain 5) Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]

CAPN5 Gene-Disease associations (from GenCC):

• CAPN5-related vitreoretinopathy

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant neovascular inflammatory vitreoretinopathy

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN5	NM_004055.5	c.165+3126G>A		intron_variant	Intron 2 of 12	ENST00000648180.1	NP_004046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN5	ENST00000648180.1	c.165+3126G>A		intron_variant	Intron 2 of 12		NM_004055.5	ENSP00000498132.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44947 AN: 151462 Hom.: 7209 Cov.: 29

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.313 AC: 275785 AN: 881618 Hom.: 49776 AF XY: 0.312 AC XY: 137228 AN XY: 439404

African (AFR) AF: 0.171 AC: 3460 AN: 20264

American (AMR) AF: 0.290 AC: 5310 AN: 18302

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 6391 AN: 15926

East Asian (EAS) AF: 0.295 AC: 9119 AN: 30944

South Asian (SAS) AF: 0.232 AC: 12583 AN: 54354

European-Finnish (FIN) AF: 0.335 AC: 9839 AN: 29358

Middle Eastern (MID) AF: 0.379 AC: 1066 AN: 2814

European-Non Finnish (NFE) AF: 0.322 AC: 215388 AN: 669480

Other (OTH) AF: 0.314 AC: 12629 AN: 40176

GnomAD4 genome AF: 0.297 AC: 44969 AN: 151580 Hom.: 7211 Cov.: 29 AF XY: 0.294 AC XY: 21718 AN XY: 73992

African (AFR) AF: 0.192 AC: 7916 AN: 41322

American (AMR) AF: 0.295 AC: 4501 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3466

East Asian (EAS) AF: 0.261 AC: 1318 AN: 5052

South Asian (SAS) AF: 0.227 AC: 1090 AN: 4794

European-Finnish (FIN) AF: 0.326 AC: 3439 AN: 10548

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24000 AN: 67840

Other (OTH) AF: 0.340 AC: 715 AN: 2102

Alfa AF: 0.339 Hom.: 1846

Bravo AF: 0.292

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.62
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7102149; hg19: chr11-76799223;