rs16975424

Positions:

• chr13-110162576-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000375820.10(COL4A1):​c.4250-134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 733,940 control chromosomes in the GnomAD database, including 8,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1375 hom., cov: 33)
  • Exomes 𝑓: 0.15 (7273 hom.)
• Consequence: COL4A1 ENST00000375820.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.303

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-110162576-A-G is Benign according to our data. Variant chr13-110162576-A-G is described in ClinVar as [Benign]. Clinvar id is 1292897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A1	NM_001845.6	c.4250-134T>C		intron_variant		ENST00000375820.10	NP_001836.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10	c.4250-134T>C		intron_variant		1	NM_001845.6	ENSP00000364979	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18731 AN: 152106 Hom.: 1379 Cov.: 33

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.153 AC: 89015 AN: 581716 Hom.: 7273 AF XY: 0.154 AC XY: 47747 AN XY: 310098

Gnomad4 AFR exome AF: 0.0409

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.123 AC: 18717 AN: 152224 Hom.: 1375 Cov.: 33 AF XY: 0.124 AC XY: 9208 AN XY: 74428

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.154

Alfa AF: 0.132 Hom.: 175

Bravo AF: 0.122

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.68

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: rs16975424; hg19: chr13-110814923;