rs35120918

chr13-110491194-G-Achr13-110491194-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001846.4(COL4A2):c.3347-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,437,422 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (10 hom., cov: 33)
  • Exomes 𝑓: 0.010 (76 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.11

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-110491194-G-A is Benign according to our data. Variant chr13-110491194-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1198088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1581/152292) while in subpopulation AFR AF= 0.0143 (593/41566). AF 95% confidence interval is 0.0133. There are 10 homozygotes in gnomad4. There are 698 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1579 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.3347-39G>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.3347-39G>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000650225.1	n.1002-39G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1579 AN: 152174 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00764 AC: 1267 AN: 165876 Hom.: 7 AF XY: 0.00758 AC XY: 670 AN XY: 88416

Gnomad AFR exome AF: 0.0154

Gnomad AMR exome AF: 0.00865

Gnomad ASJ exome AF: 0.00392

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00119

Gnomad FIN exome AF: 0.00345

Gnomad NFE exome AF: 0.0113

Gnomad OTH exome AF: 0.00895

GnomAD4 exome AF: 0.0104 AC: 13349 AN: 1285130 Hom.: 76 Cov.: 19 AF XY: 0.0101 AC XY: 6473 AN XY: 640746

Gnomad4 AFR exome AF: 0.0152

Gnomad4 AMR exome AF: 0.00871

Gnomad4 ASJ exome AF: 0.00530

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.00383

Gnomad4 NFE exome AF: 0.0120

Gnomad4 OTH exome AF: 0.00983

GnomAD4 genome AF: 0.0104 AC: 1581 AN: 152292 Hom.: 10 Cov.: 33 AF XY: 0.00937 AC XY: 698 AN XY: 74474

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00646 Hom.: 2

Bravo AF: 0.0111

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.14
Dann	Benign	0.45

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: rs35120918; hg19: chr13-111143541;