rs378601

Variant names:

• chr13-110501587-G-A
• rs378601
• NM_001846.4:c.3761-81G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110501587-G-A
• chr13-110501587-G-C
• chr13-110501587-G-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.3761-81G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,217,880 control chromosomes in the GnomAD database, including 597,546 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70055 hom., cov: 33)
  • Exomes 𝑓: 0.99 (527491 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0400
• 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 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

ENSG00000289010 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 13-110501587-G-A is Benign according to our data. Variant chr13-110501587-G-A is described in ClinVar as Benign. ClinVar VariationId is 1239667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3761-81G>A		intron_variant	Intron 40 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3761-81G>A		intron_variant	Intron 40 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145656 AN: 152180 Hom.: 70010 Cov.: 33

Gnomad AFR AF: 0.850

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.973

GnomAD4 exome AF: 0.995 AC: 1059905 AN: 1065582 Hom.: 527491 AF XY: 0.995 AC XY: 545385 AN XY: 547884

African (AFR) AF: 0.835 AC: 22100 AN: 26460

American (AMR) AF: 0.992 AC: 43246 AN: 43596

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 23353 AN: 23364

East Asian (EAS) AF: 1.00 AC: 37404 AN: 37404

South Asian (SAS) AF: 1.00 AC: 77623 AN: 77652

European-Finnish (FIN) AF: 1.00 AC: 48646 AN: 48654

Middle Eastern (MID) AF: 0.992 AC: 4481 AN: 4518

European-Non Finnish (NFE) AF: 1.00 AC: 756435 AN: 756768

Other (OTH) AF: 0.988 AC: 46617 AN: 47166

GnomAD4 genome AF: 0.957 AC: 145759 AN: 152298 Hom.: 70055 Cov.: 33 AF XY: 0.959 AC XY: 71381 AN XY: 74458

African (AFR) AF: 0.850 AC: 35290 AN: 41532

American (AMR) AF: 0.988 AC: 15124 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3468 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5164 AN: 5164

South Asian (SAS) AF: 0.999 AC: 4820 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10628

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 68008 AN: 68046

Other (OTH) AF: 0.974 AC: 2058 AN: 2114

Alfa AF: 0.935 Hom.: 25788

Bravo AF: 0.951

Asia WGS AF: 0.990 AC: 3443 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.040
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: rs378601; hg19: chr13-111153934;