rs72657934

Variant names:

• chr13-110450518-G-A
• rs72657934
• NM_001846.4:c.1339+64G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110450518-G-A
• chr13-110450518-G-T

Variant summary

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

The NM_001846.4(COL4A2):​c.1339+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,574,660 control chromosomes in the GnomAD database, including 21,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1705 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19583 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.506
• Publications: 4 publications found

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

COL4A2 Gene-Disease associations (from GenCC):

• porencephaly 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• COL4A1 or COL4A2-related cerebral small vessel disease

  Inheritance: AD Classification: MODERATE Submitted by: Illumina
• familial porencephaly

  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=-0.88).
• BP6: Variant 13-110450518-G-A is Benign according to our data. Variant chr13-110450518-G-A is described in ClinVar as Benign. ClinVar VariationId is 1232744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1339+64G>A		intron_variant	Intron 20 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1339+64G>A		intron_variant	Intron 20 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21640 AN: 152014 Hom.: 1712 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.159 AC: 226619 AN: 1422530 Hom.: 19583 AF XY: 0.158 AC XY: 111466 AN XY: 706456

African (AFR) AF: 0.114 AC: 3725 AN: 32558

American (AMR) AF: 0.102 AC: 4313 AN: 42492

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 6608 AN: 25312

East Asian (EAS) AF: 0.00428 AC: 168 AN: 39210

South Asian (SAS) AF: 0.0778 AC: 6607 AN: 84880

European-Finnish (FIN) AF: 0.143 AC: 6814 AN: 47812

Middle Eastern (MID) AF: 0.296 AC: 1670 AN: 5638

European-Non Finnish (NFE) AF: 0.172 AC: 187228 AN: 1085822

Other (OTH) AF: 0.161 AC: 9486 AN: 58806

GnomAD4 genome AF: 0.142 AC: 21644 AN: 152130 Hom.: 1705 Cov.: 32 AF XY: 0.138 AC XY: 10295 AN XY: 74362

African (AFR) AF: 0.116 AC: 4822 AN: 41506

American (AMR) AF: 0.140 AC: 2132 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 883 AN: 3468

East Asian (EAS) AF: 0.00734 AC: 38 AN: 5176

South Asian (SAS) AF: 0.0700 AC: 337 AN: 4816

European-Finnish (FIN) AF: 0.132 AC: 1396 AN: 10596

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.168 AC: 11443 AN: 67978

Other (OTH) AF: 0.169 AC: 355 AN: 2106

Alfa AF: 0.152 Hom.: 248

Bravo AF: 0.143

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.47
PhyloP100		-0.51
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

Other links and lift over

dbSNP: rs72657934; hg19: chr13-111102865; COSMIC: COSV64636451;