chr13-110503806-G-A

Variant names:

• chr13-110503806-G-A
• rs9301460
• NM_001846.4:c.4139-41G>A

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.4139-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,609,432 control chromosomes in the GnomAD database, including 110,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11531 hom., cov: 32)
  • Exomes 𝑓: 0.36 (98822 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01
• Publications: 12 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=-0.8).
• BP6: Variant 13-110503806-G-A is Benign according to our data. Variant chr13-110503806-G-A is described in ClinVar as Benign. ClinVar VariationId is 1281130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 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.4139-41G>A		intron	N/A	NP_001837.2
	COL4A2-AS1	NR_046583.1		n.187-878C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.4139-41G>A		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000649396.1		n.56G>A		non_coding_transcript_exon	Exon 1 of 3
	COL4A2	ENST00000714399.1		c.4220-41G>A		intron	N/A	ENSP00000519666.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58431 AN: 151852 Hom.: 11520 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.348 AC: 86375 AN: 248350 AF XY: 0.354

Gnomad AFR exome AF: 0.459

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.425

Gnomad NFE exome AF: 0.369

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.364 AC: 529898 AN: 1457462 Hom.: 98822 Cov.: 34 AF XY: 0.365 AC XY: 264575 AN XY: 725280

African (AFR) AF: 0.468 AC: 15587 AN: 33330

American (AMR) AF: 0.232 AC: 10324 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9363 AN: 26078

East Asian (EAS) AF: 0.182 AC: 7216 AN: 39674

South Asian (SAS) AF: 0.376 AC: 32328 AN: 86078

European-Finnish (FIN) AF: 0.420 AC: 22410 AN: 53374

Middle Eastern (MID) AF: 0.412 AC: 2365 AN: 5734

European-Non Finnish (NFE) AF: 0.368 AC: 407997 AN: 1108510

Other (OTH) AF: 0.371 AC: 22308 AN: 60204

GnomAD4 genome AF: 0.385 AC: 58471 AN: 151970 Hom.: 11531 Cov.: 32 AF XY: 0.384 AC XY: 28534 AN XY: 74290

African (AFR) AF: 0.459 AC: 19035 AN: 41450

American (AMR) AF: 0.309 AC: 4728 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3464

East Asian (EAS) AF: 0.197 AC: 1016 AN: 5146

South Asian (SAS) AF: 0.387 AC: 1869 AN: 4830

European-Finnish (FIN) AF: 0.415 AC: 4396 AN: 10584

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25050 AN: 67898

Other (OTH) AF: 0.373 AC: 786 AN: 2106

Alfa AF: 0.383 Hom.: 2598

Bravo AF: 0.375

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.55
PhyloP100		1.0
PromoterAI		-0.047	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: rs9301460; hg19: chr13-111156153; COSMIC: COSV64632958; COSMIC: COSV64632958;