chr13-110438577-G-T

Variant names:

• chr13-110438577-G-T
• rs7984100
• NM_001846.4:c.862-41G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001846.4(COL4A2):​c.862-41G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,612,554 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (18 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29
• 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: 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.006).
• BP6: Variant 13-110438577-G-T is Benign according to our data. Variant chr13-110438577-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1194936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00698 (1060/151962) while in subpopulation AFR AF = 0.0219 (907/41382). AF 95% confidence interval is 0.0207. There are 8 homozygotes in GnomAd4. There are 504 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1060 AD gene.

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.862-41G>T		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.862-41G>T		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.862-41G>T		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.862-41G>T		intron	N/A	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.00695 AC: 1056 AN: 151844 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00229 AC: 570 AN: 249442 AF XY: 0.00191

Gnomad AFR exome AF: 0.0216

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000283

Gnomad OTH exome AF: 0.00247

GnomAD4 exome AF: 0.00107 AC: 1569 AN: 1460592 Hom.: 18 Cov.: 33 AF XY: 0.00101 AC XY: 732 AN XY: 726658

African (AFR) AF: 0.0230 AC: 770 AN: 33466

American (AMR) AF: 0.00134 AC: 60 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 429 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5746

European-Non Finnish (NFE) AF: 0.000113 AC: 125 AN: 1110860

Other (OTH) AF: 0.00302 AC: 182 AN: 60356

GnomAD4 genome AF: 0.00698 AC: 1060 AN: 151962 Hom.: 8 Cov.: 33 AF XY: 0.00678 AC XY: 504 AN XY: 74284

African (AFR) AF: 0.0219 AC: 907 AN: 41382

American (AMR) AF: 0.00452 AC: 69 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67932

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00184 Hom.: 1849

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0060
DANN	Benign	0.63
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism

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: rs7984100; hg19: chr13-111090924;