rs652572

chr13-110167110-A-Gchr13-110167110-A-T

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.3949+48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,504,160 control chromosomes in the GnomAD database, including 314,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (27238 hom., cov: 31)
  • Exomes 𝑓: 0.65 (287555 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0210

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=-0.89).
• BP6: Variant 13-110167110-A-G is Benign according to our data. Variant chr13-110167110-A-G is described in ClinVar as [Benign]. Clinvar id is 1269926.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-110167110-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.3949+48T>C		intron_variant		ENST00000375820.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.3949+48T>C		intron_variant		1	NM_001845.6	P1
COL4A1	ENST00000650424.1	c.105+48T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89047 AN: 151432 Hom.: 27237 Cov.: 31

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.606

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.586

GnomAD3 exomes AF: 0.651 AC: 163568 AN: 251176 Hom.: 54120 AF XY: 0.653 AC XY: 88687 AN XY: 135808

Gnomad AFR exome AF: 0.393

Gnomad AMR exome AF: 0.715

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.652

Gnomad SAS exome AF: 0.657

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.633

GnomAD4 exome AF: 0.649 AC: 878332 AN: 1352608 Hom.: 287555 Cov.: 21 AF XY: 0.650 AC XY: 441522 AN XY: 679188

Gnomad4 AFR exome AF: 0.385

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.649

Gnomad4 SAS exome AF: 0.659

Gnomad4 FIN exome AF: 0.730

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.642

GnomAD4 genome AF: 0.588 AC: 89085 AN: 151552 Hom.: 27238 Cov.: 31 AF XY: 0.595 AC XY: 44049 AN XY: 74078

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.590

Alfa AF: 0.558 Hom.: 4079

Bravo AF: 0.577

Asia WGS AF: 0.682 AC: 2374 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 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.9
Dann	Benign	0.28

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: rs652572; hg19: chr13-110819457;