rs12873113

Positions:

• chr13-110502883-G-T

Variant summary

Our verdict is Benign. Variant got -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

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)

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3878-238G>T		intron_variant		ENST00000360467.7	NP_001837.2
COL4A2-AS1	NR_046583.1	n.232C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3878-238G>T		intron_variant		5	NM_001846.4	ENSP00000353654	P1
COL4A2-AS1	ENST00000417970.2	n.232C>A		non_coding_transcript_exon_variant	3/3	3
COL4A2	ENST00000650225.1	n.1533-238G>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.0245

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.210

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

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0446

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.209

Alfa AF: 0.223 Hom.: 6143

Bravo AF: 0.220

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.12
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs12873113; hg19: chr13-111155230;