rs7489705

Variant names:

• chr13-110445763-C-T
• rs7489705
• NM_001846.4:c.958-66C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-110445763-C-T
• chr13-110445763-C-G

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.958-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 1,560,462 control chromosomes in the GnomAD database, including 545,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (53167 hom., cov: 32)
  • Exomes 𝑓: 0.83 (492104 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.12
• Publications: 8 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=-0.92).
• BP6: Variant 13-110445763-C-T is Benign according to our data. Variant chr13-110445763-C-T is described in ClinVar as Benign. ClinVar VariationId is 1174325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 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.958-66C>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.958-66C>T		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.958-66C>T		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.958-66C>T		intron	N/A	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126886 AN: 152076 Hom.: 53130 Cov.: 32

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.842

GnomAD4 exome AF: 0.835 AC: 1175399 AN: 1408268 Hom.: 492104 AF XY: 0.835 AC XY: 587909 AN XY: 703700

African (AFR) AF: 0.862 AC: 27960 AN: 32424

American (AMR) AF: 0.707 AC: 31459 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 22934 AN: 25778

East Asian (EAS) AF: 0.683 AC: 26923 AN: 39420

South Asian (SAS) AF: 0.809 AC: 68892 AN: 85148

European-Finnish (FIN) AF: 0.785 AC: 41688 AN: 53076

Middle Eastern (MID) AF: 0.889 AC: 5038 AN: 5670

European-Non Finnish (NFE) AF: 0.848 AC: 901487 AN: 1063578

Other (OTH) AF: 0.836 AC: 49018 AN: 58660

GnomAD4 genome AF: 0.834 AC: 126975 AN: 152194 Hom.: 53167 Cov.: 32 AF XY: 0.830 AC XY: 61718 AN XY: 74394

African (AFR) AF: 0.860 AC: 35712 AN: 41520

American (AMR) AF: 0.786 AC: 12022 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3117 AN: 3472

East Asian (EAS) AF: 0.666 AC: 3445 AN: 5170

South Asian (SAS) AF: 0.803 AC: 3871 AN: 4820

European-Finnish (FIN) AF: 0.783 AC: 8288 AN: 10584

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57646 AN: 68006

Other (OTH) AF: 0.840 AC: 1775 AN: 2114

Alfa AF: 0.838 Hom.: 20574

Bravo AF: 0.832

Asia WGS AF: 0.729 AC: 2538 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	-0.92
CADD	Benign	0.24
DANN	Benign	0.31
PhyloP100		-1.1
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: rs7489705; hg19: chr13-111098110; COSMIC: COSV107471769;