rs503053

Positions:

• chr13-110179104-T-C
• chr13-110179104-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.2345-68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,535,320 control chromosomes in the GnomAD database, including 108,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (12972 hom., cov: 32)
  • Exomes 𝑓: 0.37 (95567 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.520

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 13-110179104-T-C is Benign according to our data. Variant chr13-110179104-T-C is described in ClinVar as [Benign]. Clinvar id is 1251073.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-110179104-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.2345-68A>G		intron_variant		ENST00000375820.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.2345-68A>G		intron_variant		1	NM_001845.6	P1
COL4A1	ENST00000649738.1	n.2475-68A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61911 AN: 151872 Hom.: 12943 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.369 AC: 510955 AN: 1383328 Hom.: 95567 Cov.: 22 AF XY: 0.369 AC XY: 254926 AN XY: 691386

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.408 AC: 62001 AN: 151992 Hom.: 12972 Cov.: 32 AF XY: 0.406 AC XY: 30142 AN XY: 74316

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.410

Alfa AF: 0.308 Hom.: 1138

Bravo AF: 0.415

Asia WGS AF: 0.381 AC: 1323 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.23

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: rs503053; hg19: chr13-110831451;