13-110213718-C-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.279+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,530,950 control chromosomes in the GnomAD database, including 41,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (3878 hom., cov: 31)
  • Exomes 𝑓: 0.23 (38009 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.646

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=-0.9).
• BP6: Variant 13-110213718-C-T is Benign according to our data. Variant chr13-110213718-C-T is described in ClinVar as [Benign]. Clinvar id is 1258176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.279+64G>A		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2	c.279+64G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.279+64G>A		intron_variant		1	NM_001845.6	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34321 AN: 151886 Hom.: 3875 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.232 AC: 320548 AN: 1378946 Hom.: 38009 AF XY: 0.231 AC XY: 159471 AN XY: 690680

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.204

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.226 AC: 34345 AN: 152004 Hom.: 3878 Cov.: 31 AF XY: 0.225 AC XY: 16691 AN XY: 74310

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.241

Alfa AF: 0.226 Hom.: 622

Bravo AF: 0.226

Asia WGS AF: 0.223 AC: 775 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	-0.90
Cadd	Benign	3.7
Dann	Benign	0.68

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: rs3737328; hg19: chr13-110866065; COSMIC: COSV65422564;