13-110459035-G-A

Variant names:

• chr13-110459035-G-A
• rs4773186
• NM_001846.4:c.1596+101G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):​c.1596+101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,209,436 control chromosomes in the GnomAD database, including 333,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (43170 hom., cov: 32)
  • Exomes 𝑓: 0.74 (290689 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0100
• Publications: 7 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-AS2 (HGNC:39849): (COL4A2 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-110459035-G-A is Benign according to our data. Variant chr13-110459035-G-A is described in ClinVar as Benign. ClinVar VariationId is 1293755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 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.1596+101G>A		intron	N/A	NP_001837.2
	COL4A2-AS2	NR_171022.1		n.266-749C>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.1596+101G>A		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000617564.3	TSL:6	c.*20G>A		3_prime_UTR	Exon 22 of 22	ENSP00000481492.3
	COL4A2	ENST00000714399.1		c.1677+101G>A		intron	N/A	ENSP00000519666.1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113869 AN: 151952 Hom.: 43114 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.738 AC: 780781 AN: 1057364 Hom.: 290689 Cov.: 14 AF XY: 0.737 AC XY: 383136 AN XY: 519802

African (AFR) AF: 0.790 AC: 17609 AN: 22288

American (AMR) AF: 0.763 AC: 13161 AN: 17240

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 13760 AN: 17024

East Asian (EAS) AF: 0.490 AC: 15603 AN: 31814

South Asian (SAS) AF: 0.657 AC: 36661 AN: 55832

European-Finnish (FIN) AF: 0.615 AC: 25808 AN: 41954

Middle Eastern (MID) AF: 0.810 AC: 2496 AN: 3082

European-Non Finnish (NFE) AF: 0.756 AC: 621906 AN: 822748

Other (OTH) AF: 0.744 AC: 33777 AN: 45382

GnomAD4 genome AF: 0.750 AC: 113981 AN: 152072 Hom.: 43170 Cov.: 32 AF XY: 0.740 AC XY: 54996 AN XY: 74312

African (AFR) AF: 0.792 AC: 32823 AN: 41460

American (AMR) AF: 0.779 AC: 11921 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2862 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2586 AN: 5144

South Asian (SAS) AF: 0.652 AC: 3143 AN: 4818

European-Finnish (FIN) AF: 0.603 AC: 6380 AN: 10578

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51596 AN: 67990

Other (OTH) AF: 0.764 AC: 1610 AN: 2106

Alfa AF: 0.767 Hom.: 55265

Bravo AF: 0.762

Asia WGS AF: 0.595 AC: 2068 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.91
CADD	Benign	0.63
DANN	Benign	0.51
PhyloP100		-0.010
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: rs4773186; hg19: chr13-111111382;