rs9588179

Variant names:

• chr13-110473400-C-A
• rs9588179
• NM_001846.4:c.2425+250C>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.2425+250C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 469,094 control chromosomes in the GnomAD database, including 1,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (1156 hom., cov: 33)
  • Exomes 𝑓: 0.017 (296 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.347
• Publications: 3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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=-0.84).
• BP6: Variant 13-110473400-C-A is Benign according to our data. Variant chr13-110473400-C-A is described in ClinVar as Benign. ClinVar VariationId is 1270352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.2425+250C>A		intron	N/A	NP_001837.2	P08572

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.2425+250C>A		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.2506+250C>A		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.2425+250C>A		intron	N/A	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10723 AN: 152142 Hom.: 1150 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.0368

Gnomad SAS AF: 0.0704

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.0535

GnomAD4 exome AF: 0.0175 AC: 5533 AN: 316834 Hom.: 296 AF XY: 0.0183 AC XY: 2993 AN XY: 163788

African (AFR) AF: 0.230 AC: 1721 AN: 7486

American (AMR) AF: 0.0200 AC: 205 AN: 10234

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 179 AN: 10770

East Asian (EAS) AF: 0.0551 AC: 1218 AN: 22088

South Asian (SAS) AF: 0.0616 AC: 1379 AN: 22400

European-Finnish (FIN) AF: 0.000168 AC: 4 AN: 23764

Middle Eastern (MID) AF: 0.0149 AC: 23 AN: 1542

European-Non Finnish (NFE) AF: 0.00143 AC: 285 AN: 198688

Other (OTH) AF: 0.0261 AC: 519 AN: 19862

GnomAD4 genome AF: 0.0707 AC: 10758 AN: 152260 Hom.: 1156 Cov.: 33 AF XY: 0.0681 AC XY: 5072 AN XY: 74464

African (AFR) AF: 0.229 AC: 9487 AN: 41508

American (AMR) AF: 0.0297 AC: 455 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3470

East Asian (EAS) AF: 0.0367 AC: 190 AN: 5178

South Asian (SAS) AF: 0.0704 AC: 340 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00160 AC: 109 AN: 68032

Other (OTH) AF: 0.0529 AC: 112 AN: 2116

Alfa AF: 0.0540 Hom.: 79

Bravo AF: 0.0789

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

ClinVar submissions

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	-0.84
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-0.35
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: rs9588179; hg19: chr13-111125747;