13-110503364-C-T

Variant names:

• chr13-110503364-C-T
• rs4773198
• NM_001846.4:c.4040-19C>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.4040-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,591,204 control chromosomes in the GnomAD database, including 107,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10803 hom., cov: 34)
  • Exomes 𝑓: 0.36 (96506 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.484
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-110503364-C-T is Benign according to our data. Variant chr13-110503364-C-T is described in ClinVar as Benign. ClinVar VariationId is 1165076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 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.4040-19C>T		intron	N/A	NP_001837.2
	COL4A2-AS1	NR_046583.1		n.187-436G>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.4040-19C>T		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.4121-19C>T		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.4040-19C>T		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56828 AN: 151988 Hom.: 10796 Cov.: 34

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.370

GnomAD2 exomes AF: 0.347 AC: 76131 AN: 219220 AF XY: 0.354

Gnomad AFR exome AF: 0.425

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.363 AC: 521770 AN: 1439098 Hom.: 96506 Cov.: 33 AF XY: 0.364 AC XY: 259933 AN XY: 714638

African (AFR) AF: 0.432 AC: 14097 AN: 32630

American (AMR) AF: 0.233 AC: 9334 AN: 40056

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 8768 AN: 25134

East Asian (EAS) AF: 0.183 AC: 7166 AN: 39198

South Asian (SAS) AF: 0.375 AC: 31364 AN: 83660

European-Finnish (FIN) AF: 0.420 AC: 22091 AN: 52584

Middle Eastern (MID) AF: 0.440 AC: 2492 AN: 5670

European-Non Finnish (NFE) AF: 0.368 AC: 404628 AN: 1100880

Other (OTH) AF: 0.368 AC: 21830 AN: 59286

GnomAD4 genome AF: 0.374 AC: 56861 AN: 152106 Hom.: 10803 Cov.: 34 AF XY: 0.374 AC XY: 27775 AN XY: 74362

African (AFR) AF: 0.424 AC: 17588 AN: 41496

American (AMR) AF: 0.301 AC: 4611 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1186 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1030 AN: 5168

South Asian (SAS) AF: 0.386 AC: 1862 AN: 4820

European-Finnish (FIN) AF: 0.417 AC: 4416 AN: 10598

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.368 AC: 25013 AN: 67942

Other (OTH) AF: 0.368 AC: 778 AN: 2116

Alfa AF: 0.366 Hom.: 34892

Bravo AF: 0.363

Asia WGS AF: 0.295 AC: 1028 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.060
DANN	Benign	0.66
PhyloP100		-0.48
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: rs4773198; hg19: chr13-111155711; COSMIC: COSV64624987; COSMIC: COSV64624987;