rs4771683

Variant names:

• chr13-110504152-C-T
• rs4771683
• NM_001846.4:c.4290C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-110504152-C-T
• chr13-110504152-C-A
• chr13-110504152-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001846.4(COL4A2):​c.4290C>T​(p.Phe1430Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,614,066 control chromosomes in the GnomAD database, including 791,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68606 hom., cov: 33)
  • Exomes 𝑓: 0.99 (722545 hom.)
• Consequence: COL4A2 NM_001846.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.463
• Publications: 19 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-AS1 (HGNC:40156): (COL4A2 antisense RNA 1)

ENSG00000289010 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 13-110504152-C-T is Benign according to our data. Variant chr13-110504152-C-T is described in ClinVar as Benign. ClinVar VariationId is 1165352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.463 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.4290C>T	p.Phe1430Phe	synonymous	Exon 45 of 48	NP_001837.2	P08572
	COL4A2-AS1	NR_046583.1		n.187-1224G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.4290C>T	p.Phe1430Phe	synonymous	Exon 45 of 48	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.4371C>T	p.Phe1457Phe	synonymous	Exon 46 of 49	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.4290C>T	p.Phe1430Phe	synonymous	Exon 45 of 48	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143940 AN: 152158 Hom.: 68563 Cov.: 33

Gnomad AFR AF: 0.813

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.964

GnomAD2 exomes AF: 0.986 AC: 245913 AN: 249450 AF XY: 0.989

Gnomad AFR exome AF: 0.813

Gnomad AMR exome AF: 0.991

Gnomad ASJ exome AF: 0.983

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.993

GnomAD4 exome AF: 0.994 AC: 1452750 AN: 1461790 Hom.: 722545 Cov.: 46 AF XY: 0.995 AC XY: 723253 AN XY: 727202

African (AFR) AF: 0.805 AC: 26935 AN: 33474

American (AMR) AF: 0.990 AC: 44287 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 25670 AN: 26130

East Asian (EAS) AF: 1.00 AC: 39699 AN: 39700

South Asian (SAS) AF: 0.999 AC: 86186 AN: 86256

European-Finnish (FIN) AF: 1.00 AC: 53372 AN: 53380

Middle Eastern (MID) AF: 0.991 AC: 5714 AN: 5768

European-Non Finnish (NFE) AF: 0.999 AC: 1111377 AN: 1111966

Other (OTH) AF: 0.985 AC: 59510 AN: 60394

GnomAD4 genome AF: 0.946 AC: 144038 AN: 152276 Hom.: 68606 Cov.: 33 AF XY: 0.948 AC XY: 70554 AN XY: 74440

African (AFR) AF: 0.813 AC: 33763 AN: 41534

American (AMR) AF: 0.983 AC: 15049 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.983 AC: 3410 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5158 AN: 5158

South Asian (SAS) AF: 0.999 AC: 4824 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10630

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67965 AN: 68020

Other (OTH) AF: 0.964 AC: 2038 AN: 2114

Alfa AF: 0.973 Hom.: 37395

Bravo AF: 0.939

Asia WGS AF: 0.987 AC: 3432 AN: 3478

EpiCase AF: 0.999

EpiControl AF: 0.999

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.9
DANN	Benign	0.78
PhyloP100		-0.46
PromoterAI		-0.029	Neutral
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: rs4771683; hg19: chr13-111156499; COSMIC: COSV64631754; COSMIC: COSV64631754;