rs7987982

chr13-110278964-T-Cchr13-110278964-T-G

Variant summary

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

The NM_001845.6(COL4A1):c.84+27980A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,112 control chromosomes in the GnomAD database, including 3,752 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 0.20 (3752 hom., cov: 32)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.84+27980A>G		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2	c.84+27980A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.84+27980A>G		intron_variant		1	NM_001845.6	P1
COL4A1	ENST00000543140.6	c.84+27980A>G		intron_variant		1
COL4A1	ENST00000615732.2	c.-109+19641A>G		intron_variant		5
COL4A1	ENST00000649738.1	n.214+27980A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29938 AN: 151994 Hom.: 3743 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.197 AC: 29993 AN: 152112 Hom.: 3752 Cov.: 32 AF XY: 0.192 AC XY: 14282 AN XY: 74366

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0493

Gnomad4 SAS AF: 0.0928

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.196

Alfa AF: 0.144 Hom.: 3597

Bravo AF: 0.206

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.065
Dann	Benign	0.22

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: rs7987982; hg19: chr13-110931311;