rs2305080

chr13-110186356-T-C

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.1897+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,611,298 control chromosomes in the GnomAD database, including 107,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (9921 hom., cov: 33)
  • Exomes 𝑓: 0.36 (97759 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.712

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 13-110186356-T-C is Benign according to our data. Variant chr13-110186356-T-C is described in ClinVar as [Benign]. Clinvar id is 1261039.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-110186356-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.1897+29A>G		intron_variant		ENST00000375820.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.1897+29A>G		intron_variant		1	NM_001845.6	P1
COL4A1	ENST00000649738.1	n.2027+29A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54848 AN: 152012 Hom.: 9904 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.370

GnomAD3 exomes AF: 0.366 AC: 90701 AN: 247764 Hom.: 17052 AF XY: 0.363 AC XY: 48936 AN XY: 134836

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.304

Gnomad EAS exome AF: 0.468

Gnomad SAS exome AF: 0.337

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.353

GnomAD4 exome AF: 0.364 AC: 531200 AN: 1459168 Hom.: 97759 Cov.: 37 AF XY: 0.363 AC XY: 263589 AN XY: 725918

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.468

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.365

Gnomad4 OTH exome AF: 0.362

GnomAD4 genome AF: 0.361 AC: 54908 AN: 152130 Hom.: 9921 Cov.: 33 AF XY: 0.360 AC XY: 26788 AN XY: 74346

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.375

Alfa AF: 0.352 Hom.: 1976

Bravo AF: 0.364

Asia WGS AF: 0.418 AC: 1451 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	0.048
Dann	Benign	0.29

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: rs2305080; hg19: chr13-110838703; COSMIC: COSV65429663; COSMIC: COSV65429663;