rs1975514

chr13-110176544-T-Cchr13-110176544-T-G

Variant summary

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

The NM_001845.6(COL4A1):c.2969-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,596,810 control chromosomes in the GnomAD database, including 104,856 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (8872 hom., cov: 32)
  • Exomes 𝑓: 0.36 (95984 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.279

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=-0.82).
• BP6: Variant 13-110176544-T-C is Benign according to our data. Variant chr13-110176544-T-C is described in ClinVar as [Benign]. Clinvar id is 1293324.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-110176544-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.2969-31A>G		intron_variant		ENST00000375820.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.2969-31A>G		intron_variant		1	NM_001845.6	P1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51665 AN: 151916 Hom.: 8859 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.354

GnomAD3 exomes AF: 0.356 AC: 89231 AN: 250612 Hom.: 16238 AF XY: 0.357 AC XY: 48372 AN XY: 135490

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.302

Gnomad SAS exome AF: 0.368

Gnomad FIN exome AF: 0.351

Gnomad NFE exome AF: 0.365

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.362 AC: 523171 AN: 1444776 Hom.: 95984 Cov.: 28 AF XY: 0.362 AC XY: 260885 AN XY: 719874

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.340 AC: 51718 AN: 152034 Hom.: 8872 Cov.: 32 AF XY: 0.340 AC XY: 25290 AN XY: 74314

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.359

Alfa AF: 0.281 Hom.: 1548

Bravo AF: 0.338

Asia WGS AF: 0.362 AC: 1256 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

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.61
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1975514; hg19: chr13-110828891; COSMIC: COSV65430826;