rs1049931

Variant names:

• chr13-110512748-A-G
• rs1049931
• NM_001846.4:c.*557A>G

Variant summary

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

The ENST00000360467.7(COL4A2):​c.*557A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 155,224 control chromosomes in the GnomAD database, including 13,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12890 hom., cov: 33)
  • Exomes 𝑓: 0.48 (369 hom.)
• Consequence: COL4A2 ENST00000360467.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00900
• Publications: 10 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

ENSG00000289010 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-110512748-A-G is Benign according to our data. Variant chr13-110512748-A-G is described in ClinVar as Benign. ClinVar VariationId is 311209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360467.7. 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.*557A>G		3_prime_UTR	Exon 48 of 48	NP_001837.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.*557A>G		3_prime_UTR	Exon 48 of 48	ENSP00000353654.5
	COL4A2	ENST00000648222.1		n.1384A>G		non_coding_transcript_exon	Exon 1 of 1
	COL4A2	ENST00000650225.1		n.3351A>G		non_coding_transcript_exon	Exon 19 of 19

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61777 AN: 152064 Hom.: 12891 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.481 AC: 1464 AN: 3042 Hom.: 369 Cov.: 0 AF XY: 0.475 AC XY: 717 AN XY: 1510

African (AFR) AF: 0.393 AC: 11 AN: 28

American (AMR) AF: 0.430 AC: 116 AN: 270

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 12 AN: 28

East Asian (EAS) AF: 0.143 AC: 2 AN: 14

South Asian (SAS) AF: 0.386 AC: 61 AN: 158

European-Finnish (FIN) AF: 0.403 AC: 29 AN: 72

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.496 AC: 1125 AN: 2266

Other (OTH) AF: 0.525 AC: 106 AN: 202

GnomAD4 genome AF: 0.406 AC: 61798 AN: 152182 Hom.: 12890 Cov.: 33 AF XY: 0.404 AC XY: 30047 AN XY: 74400

African (AFR) AF: 0.324 AC: 13452 AN: 41504

American (AMR) AF: 0.448 AC: 6845 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3472

East Asian (EAS) AF: 0.195 AC: 1010 AN: 5178

South Asian (SAS) AF: 0.380 AC: 1837 AN: 4830

European-Finnish (FIN) AF: 0.421 AC: 4465 AN: 10594

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31433 AN: 67992

Other (OTH) AF: 0.402 AC: 849 AN: 2112

Alfa AF: 0.444 Hom.: 19096

Bravo AF: 0.404

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Porencephaly 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.50
PhyloP100		-0.0090
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1049931; hg19: chr13-111165095;