chr13-110195219-C-T

Position:

• chr13-110195219-C-T

Variant summary

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

The ENST00000375820.10(COL4A1):​c.1286-101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 945,432 control chromosomes in the GnomAD database, including 4,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1451 hom., cov: 32)
  • Exomes 𝑓: 0.083 (3319 hom.)
• Consequence: COL4A1 ENST00000375820.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17

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=-0.94).
• BP6: Variant 13-110195219-C-T is Benign according to our data. Variant chr13-110195219-C-T is described in ClinVar as [Benign]. Clinvar id is 1293369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110195219-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A1	NM_001845.6	c.1286-101G>A		intron_variant		ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2	c.1286-101G>A		intron_variant			NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10	c.1286-101G>A		intron_variant		1	NM_001845.6	ENSP00000364979	P1
COL4A1	ENST00000543140.6	c.1286-101G>A		intron_variant		1		ENSP00000443348
COL4A1	ENST00000649738.1	n.1416-101G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18201 AN: 152024 Hom.: 1446 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0761

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0827 AC: 65642 AN: 793290 Hom.: 3319 AF XY: 0.0813 AC XY: 33740 AN XY: 414944

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.0282

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.0706

Gnomad4 FIN exome AF: 0.0626

Gnomad4 NFE exome AF: 0.0749

Gnomad4 OTH exome AF: 0.0857

GnomAD4 genome AF: 0.120 AC: 18247 AN: 152142 Hom.: 1451 Cov.: 32 AF XY: 0.118 AC XY: 8762 AN XY: 74376

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0696

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0761

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0890 Hom.: 127

Bravo AF: 0.129

Asia WGS AF: 0.107 AC: 371 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 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.43

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: rs9588112; hg19: chr13-110847566;