rs4773144

Variant names:

• chr13-110308365-A-G
• rs4773144
• NM_001846.4:c.99+242A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-110308365-A-G
• chr13-110308365-A-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.99+242A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,942 control chromosomes in the GnomAD database, including 13,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.42 (13434 hom., cov: 32)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0400
• Publications: 119 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=-0.86).
• BP6: Variant 13-110308365-A-G is Benign according to our data. Variant chr13-110308365-A-G is described in ClinVar as Benign. ClinVar VariationId is 1254326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.438 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.99+242A>G		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.99+242A>G		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.99+242A>G		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.99+242A>G		intron	N/A	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63537 AN: 151822 Hom.: 13410 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.461

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.419 AC: 63603 AN: 151942 Hom.: 13434 Cov.: 32 AF XY: 0.417 AC XY: 30991 AN XY: 74256

African (AFR) AF: 0.384 AC: 15926 AN: 41444

American (AMR) AF: 0.447 AC: 6822 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2001 AN: 5136

South Asian (SAS) AF: 0.409 AC: 1970 AN: 4812

European-Finnish (FIN) AF: 0.407 AC: 4288 AN: 10540

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29510 AN: 67962

Other (OTH) AF: 0.461 AC: 968 AN: 2102

Alfa AF: 0.430 Hom.: 51166

Bravo AF: 0.419

Asia WGS AF: 0.392 AC: 1364 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	-0.86
CADD	Benign	6.9
DANN	Benign	0.42
PhyloP100		0.040
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: rs4773144; hg19: chr13-110960712;