13-110172917-G-T

Position:

• chr13-110172917-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001845.6(COL4A1):​c.3506-147C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 731,658 control chromosomes in the GnomAD database, including 8,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1424 hom., cov: 33)
  • Exomes 𝑓: 0.14 (7066 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.15

Genes affected

COL4A1 (HGNC:2202): (collagen type IV alpha 1 chain) This gene encodes a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. This gene shares a bidirectional promoter with a paralogous gene on the opposite strand. The protein consists of an amino-terminal 7S domain, a triple-helix forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins. In addition, proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as arresten, which has anti-angiogenic and tumor suppressor properties. Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-110172917-G-T is Benign according to our data. Variant chr13-110172917-G-T is described in ClinVar as [Benign]. Clinvar id is 1251886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A1	NM_001845.6	c.3506-147C>A		intron_variant		ENST00000375820.10	NP_001836.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10	c.3506-147C>A		intron_variant		1	NM_001845.6	ENSP00000364979.4

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18146 AN: 152100 Hom.: 1425 Cov.: 33

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.0969

GnomAD4 exome AF: 0.144 AC: 83484 AN: 579440 Hom.: 7066 AF XY: 0.145 AC XY: 45135 AN XY: 310604

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.000273

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.119 AC: 18141 AN: 152218 Hom.: 1424 Cov.: 33 AF XY: 0.123 AC XY: 9124 AN XY: 74410

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.0959

Alfa AF: 0.140 Hom.: 943

Bravo AF: 0.104

Asia WGS AF: 0.0380 AC: 137 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.030
DANN	Benign	0.24

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: rs17517598; hg19: chr13-110825264;