13-110502883-G-T

Variant names:

• chr13-110502883-G-T
• rs12873113
• NM_001846.4:c.3878-238G>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.3878-238G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 458,422 control chromosomes in the GnomAD database, including 10,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3778 hom., cov: 33)
  • Exomes 𝑓: 0.20 (6688 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.66
• Publications: 5 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=-0.94).
• BP6: Variant 13-110502883-G-T is Benign according to our data. Variant chr13-110502883-G-T is described in ClinVar as Benign. ClinVar VariationId is 1227273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.3878-238G>T		intron	N/A	NP_001837.2
	COL4A2-AS1	NR_046583.1		n.232C>A		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.3878-238G>T		intron	N/A	ENSP00000353654.5
	COL4A2-AS1	ENST00000417970.2	TSL:3	n.232C>A		non_coding_transcript_exon	Exon 3 of 3
	COL4A2	ENST00000714399.1		c.3959-238G>T		intron	N/A	ENSP00000519666.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32888 AN: 152066 Hom.: 3778 Cov.: 33

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.199 AC: 60925 AN: 306238 Hom.: 6688 Cov.: 3 AF XY: 0.200 AC XY: 31961 AN XY: 160170

African (AFR) AF: 0.255 AC: 1996 AN: 7822

American (AMR) AF: 0.161 AC: 1444 AN: 8966

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 2167 AN: 10038

East Asian (EAS) AF: 0.0245 AC: 452 AN: 18484

South Asian (SAS) AF: 0.205 AC: 6475 AN: 31568

European-Finnish (FIN) AF: 0.137 AC: 2584 AN: 18852

Middle Eastern (MID) AF: 0.275 AC: 386 AN: 1406

European-Non Finnish (NFE) AF: 0.218 AC: 41535 AN: 190622

Other (OTH) AF: 0.210 AC: 3886 AN: 18480

GnomAD4 genome AF: 0.216 AC: 32891 AN: 152184 Hom.: 3778 Cov.: 33 AF XY: 0.209 AC XY: 15565 AN XY: 74418

African (AFR) AF: 0.264 AC: 10960 AN: 41482

American (AMR) AF: 0.178 AC: 2722 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3472

East Asian (EAS) AF: 0.0446 AC: 231 AN: 5180

South Asian (SAS) AF: 0.207 AC: 1001 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1387 AN: 10616

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15128 AN: 67996

Other (OTH) AF: 0.209 AC: 441 AN: 2112

Alfa AF: 0.221 Hom.: 9215

Bravo AF: 0.220

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.94
CADD	Benign	0.12
DANN	Benign	0.64
PhyloP100		-2.7
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: rs12873113; hg19: chr13-111155230;