rs41275106

chr13-110242803-A-Gchr13-110242803-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.85-69T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,525,936 control chromosomes in the GnomAD database, including 21,998 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2182 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19816 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0200

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=-0.91).
• BP6: Variant 13-110242803-A-G is Benign according to our data. Variant chr13-110242803-A-G is described in ClinVar as [Benign]. Clinvar id is 1242718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.85-69T>C		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2	c.85-69T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.85-69T>C		intron_variant		1	NM_001845.6	P1
COL4A1	ENST00000543140.6	c.85-69T>C		intron_variant		1
COL4A1	ENST00000615732.2	c.-108-69T>C		intron_variant		5
COL4A1	ENST00000649738.1	n.215-69T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.164 AC: 25007 AN: 152120 Hom.: 2183 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00768

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.164 AC: 225721 AN: 1373698 Hom.: 19816 AF XY: 0.166 AC XY: 114144 AN XY: 688354

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.0694

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.00536

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.164 AC: 25029 AN: 152238 Hom.: 2182 Cov.: 33 AF XY: 0.160 AC XY: 11889 AN XY: 74422

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00789

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.151

Alfa AF: 0.163 Hom.: 271

Bravo AF: 0.163

Asia WGS AF: 0.0930 AC: 327 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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.3
Dann	Benign	0.26

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: rs41275106; hg19: chr13-110895150;