rs7983487

Variant names:

• chr13-110438507-A-G
• rs7983487
• NM_001846.4:c.862-111A>G

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.862-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,399,656 control chromosomes in the GnomAD database, including 72,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11005 hom., cov: 33)
  • Exomes 𝑓: 0.31 (61534 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.372
• Publications: 3 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 Gene-Disease associations (from GenCC):

• porencephaly 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• COL4A1 or COL4A2-related cerebral small vessel disease

  Inheritance: AD Classification: MODERATE Submitted by: Illumina
• familial porencephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 13-110438507-A-G is Benign according to our data. Variant chr13-110438507-A-G is described in ClinVar as Benign. ClinVar VariationId is 1242395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.862-111A>G		intron_variant	Intron 14 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.862-111A>G		intron_variant	Intron 14 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55283 AN: 152024 Hom.: 10999 Cov.: 33

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.371

GnomAD2 exomes AF: 0.300 AC: 74190 AN: 247392 AF XY: 0.300

Gnomad AFR exome AF: 0.545

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.471

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.306 AC: 381546 AN: 1247514 Hom.: 61534 Cov.: 18 AF XY: 0.305 AC XY: 192758 AN XY: 631810

African (AFR) AF: 0.544 AC: 15787 AN: 29038

American (AMR) AF: 0.216 AC: 9563 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 11544 AN: 24750

East Asian (EAS) AF: 0.116 AC: 4482 AN: 38602

South Asian (SAS) AF: 0.285 AC: 23289 AN: 81790

European-Finnish (FIN) AF: 0.290 AC: 15334 AN: 52848

Middle Eastern (MID) AF: 0.490 AC: 2566 AN: 5240

European-Non Finnish (NFE) AF: 0.307 AC: 281252 AN: 917600

Other (OTH) AF: 0.333 AC: 17729 AN: 53284

GnomAD4 genome AF: 0.364 AC: 55323 AN: 152142 Hom.: 11005 Cov.: 33 AF XY: 0.358 AC XY: 26642 AN XY: 74378

African (AFR) AF: 0.534 AC: 22178 AN: 41504

American (AMR) AF: 0.309 AC: 4725 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1586 AN: 3468

East Asian (EAS) AF: 0.128 AC: 661 AN: 5158

South Asian (SAS) AF: 0.267 AC: 1289 AN: 4824

European-Finnish (FIN) AF: 0.290 AC: 3071 AN: 10604

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20658 AN: 67982

Other (OTH) AF: 0.372 AC: 785 AN: 2110

Alfa AF: 0.357 Hom.: 2031

Bravo AF: 0.375

Asia WGS AF: 0.240 AC: 836 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

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		-0.37
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: rs7983487; hg19: chr13-111090854; COSMIC: COSV64626123;