chr13-110438677-C-T

Variant names:

• chr13-110438677-C-T
• rs7983979
• NM_001846.4:c.912+9C>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.912+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,614,062 control chromosomes in the GnomAD database, including 2,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (796 hom., cov: 33)
  • Exomes 𝑓: 0.040 (1851 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.64
• Publications: 7 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=-0.97).
• BP6: Variant 13-110438677-C-T is Benign according to our data. Variant chr13-110438677-C-T is described in ClinVar as Benign. ClinVar VariationId is 311115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 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.912+9C>T		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.912+9C>T		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.912+9C>T		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.912+9C>T		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12354 AN: 152112 Hom.: 793 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.0892

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0614

GnomAD2 exomes AF: 0.0564 AC: 14082 AN: 249562 AF XY: 0.0563

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.0384

Gnomad ASJ exome AF: 0.0252

Gnomad EAS exome AF: 0.0767

Gnomad FIN exome AF: 0.0759

Gnomad NFE exome AF: 0.0311

Gnomad OTH exome AF: 0.0429

GnomAD4 exome AF: 0.0403 AC: 58908 AN: 1461832 Hom.: 1851 Cov.: 33 AF XY: 0.0413 AC XY: 30061 AN XY: 727220

African (AFR) AF: 0.187 AC: 6253 AN: 33476

American (AMR) AF: 0.0412 AC: 1843 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0269 AC: 703 AN: 26136

East Asian (EAS) AF: 0.0724 AC: 2874 AN: 39700

South Asian (SAS) AF: 0.0918 AC: 7922 AN: 86254

European-Finnish (FIN) AF: 0.0726 AC: 3878 AN: 53414

Middle Eastern (MID) AF: 0.0510 AC: 294 AN: 5768

European-Non Finnish (NFE) AF: 0.0290 AC: 32293 AN: 1111966

Other (OTH) AF: 0.0472 AC: 2848 AN: 60394

GnomAD4 genome AF: 0.0813 AC: 12374 AN: 152230 Hom.: 796 Cov.: 33 AF XY: 0.0830 AC XY: 6174 AN XY: 74424

African (AFR) AF: 0.181 AC: 7513 AN: 41534

American (AMR) AF: 0.0580 AC: 887 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 106 AN: 3472

East Asian (EAS) AF: 0.0639 AC: 331 AN: 5182

South Asian (SAS) AF: 0.0895 AC: 432 AN: 4826

European-Finnish (FIN) AF: 0.0781 AC: 828 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0311 AC: 2113 AN: 68004

Other (OTH) AF: 0.0608 AC: 128 AN: 2106

Alfa AF: 0.0436 Hom.: 457

Bravo AF: 0.0829

Asia WGS AF: 0.0780 AC: 272 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Porencephaly 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.076
DANN	Benign	0.46
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: rs7983979; hg19: chr13-111091024; COSMIC: COSV64631995;