rs1961495

Positions:

• chr13-110229026-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001845.6(COL4A1):​c.144+13649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,116 control chromosomes in the GnomAD database, including 1,656 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1656 hom., cov: 33)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A1	NM_001845.6	c.144+13649G>A		intron_variant		ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2	c.144+13649G>A		intron_variant			NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10	c.144+13649G>A		intron_variant		1	NM_001845.6	ENSP00000364979	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21316 AN: 151998 Hom.: 1656 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 21339 AN: 152116 Hom.: 1656 Cov.: 33 AF XY: 0.142 AC XY: 10533 AN XY: 74338

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.158

Alfa AF: 0.128 Hom.: 505

Bravo AF: 0.150

Asia WGS AF: 0.248 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.72

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: rs1961495; hg19: chr13-110881373;