chr13-110306784-A-G

Position:

• chr13-110306784-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001845.6(COL4A1):​c.84+160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,252 control chromosomes in the GnomAD database, including 1,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.14 (1731 hom., cov: 33)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.811

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]

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-110306784-A-G is Benign according to our data. Variant chr13-110306784-A-G is described in ClinVar as [Benign]. Clinvar id is 1264557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.84+160T>C		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2	c.84+160T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.84+160T>C		intron_variant		1	NM_001845.6	P1
COL4A1	ENST00000543140.6	c.84+160T>C		intron_variant		1
COL4A2	ENST00000400163.7	c.-45+841A>G		intron_variant		5
COL4A1	ENST00000649738.1	n.214+160T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21577 AN: 152138 Hom.: 1727 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.177

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21604 AN: 152252 Hom.: 1731 Cov.: 33 AF XY: 0.142 AC XY: 10608 AN XY: 74450

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.175

Alfa AF: 0.135 Hom.: 299

Bravo AF: 0.153

Asia WGS AF: 0.204 AC: 706 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.86
CADD	Benign	0.66
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs12429420; hg19: chr13-110959131;