rs11839527

Variant names:

• chr13-110485141-G-A
• rs11839527
• NM_001846.4:c.3025+114G>A

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.3025+114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 955,290 control chromosomes in the GnomAD database, including 8,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1122 hom., cov: 31)
  • Exomes 𝑓: 0.13 (7264 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.62
• Publications: 5 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=-1.07).
• BP6: Variant 13-110485141-G-A is Benign according to our data. Variant chr13-110485141-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.3025+114G>A		intron	N/A	NP_001837.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.3025+114G>A		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.3106+114G>A		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.3025+114G>A		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18825 AN: 152030 Hom.: 1122 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.131 AC: 105501 AN: 803142 Hom.: 7264 AF XY: 0.131 AC XY: 52022 AN XY: 398418

African (AFR) AF: 0.120 AC: 2311 AN: 19322

American (AMR) AF: 0.116 AC: 2180 AN: 18832

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 1420 AN: 14766

East Asian (EAS) AF: 0.107 AC: 3411 AN: 31922

South Asian (SAS) AF: 0.113 AC: 4735 AN: 41748

European-Finnish (FIN) AF: 0.118 AC: 4654 AN: 39280

Middle Eastern (MID) AF: 0.0906 AC: 236 AN: 2604

European-Non Finnish (NFE) AF: 0.137 AC: 81982 AN: 598168

Other (OTH) AF: 0.125 AC: 4572 AN: 36500

GnomAD4 genome AF: 0.124 AC: 18850 AN: 152148 Hom.: 1122 Cov.: 31 AF XY: 0.124 AC XY: 9228 AN XY: 74378

African (AFR) AF: 0.120 AC: 4972 AN: 41504

American (AMR) AF: 0.106 AC: 1624 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3472

East Asian (EAS) AF: 0.158 AC: 814 AN: 5168

South Asian (SAS) AF: 0.116 AC: 558 AN: 4822

European-Finnish (FIN) AF: 0.108 AC: 1137 AN: 10574

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8923 AN: 67998

Other (OTH) AF: 0.118 AC: 249 AN: 2114

Alfa AF: 0.128 Hom.: 1593

Bravo AF: 0.126

Asia WGS AF: 0.114 AC: 395 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.52
DANN	Benign	0.69
PhyloP100		-1.6
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: rs11839527; hg19: chr13-111137488; COSMIC: COSV107471775;