rs4512966

Variant names:

• chr13-110429711-T-C
• rs4512966
• NM_001846.4:c.478-174T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-110429711-T-C
• chr13-110429711-T-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.478-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,082 control chromosomes in the GnomAD database, including 19,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.51 (19911 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.102
• Publications: 9 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), G2P, Ambry Genetics
• 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=-0.98).
• BP6: Variant 13-110429711-T-C is Benign according to our data. Variant chr13-110429711-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 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.478-174T>C		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.478-174T>C		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000619688.3	TSL:6	c.*1077T>C		3_prime_UTR	Exon 7 of 7	ENSP00000496868.2	A0A3B3IRV2
	COL4A2	ENST00000714399.1		c.478-174T>C		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77233 AN: 151964 Hom.: 19891 Cov.: 33

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.508 AC: 77314 AN: 152082 Hom.: 19911 Cov.: 33 AF XY: 0.505 AC XY: 37557 AN XY: 74342

African (AFR) AF: 0.570 AC: 23655 AN: 41488

American (AMR) AF: 0.484 AC: 7405 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2131 AN: 5174

South Asian (SAS) AF: 0.476 AC: 2290 AN: 4812

European-Finnish (FIN) AF: 0.447 AC: 4734 AN: 10584

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33385 AN: 67948

Other (OTH) AF: 0.507 AC: 1072 AN: 2114

Alfa AF: 0.499 Hom.: 80125

Bravo AF: 0.515

Asia WGS AF: 0.443 AC: 1546 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	-0.98
CADD	Benign	3.7
DANN	Benign	0.53
PhyloP100		0.10
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4512966;

hg19: chr13-111082058;