13-110194880-G-T

Variant names:

• chr13-110194880-G-T
• rs505050
• NM_001845.6:c.1381+143C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000375820.10(COL4A1):​c.1381+143C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 714,006 control chromosomes in the GnomAD database, including 199,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (40142 hom., cov: 31)
  • Exomes 𝑓: 0.75 (159223 hom.)
• Consequence: COL4A1 ENST00000375820.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.81
• Publications: 4 publications found

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]

COL4A1 Gene-Disease associations (from GenCC):

• brain small vessel disease 1 with or without ocular anomalies

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, PanelApp Australia, Orphanet, Genomics England PanelApp
• autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Ambry Genetics
• microangiopathy and leukoencephalopathy, pontine, autosomal dominant

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• familial porencephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pontine autosomal dominant microangiopathy with leukoencephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinal arterial tortuosity

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 13-110194880-G-T is Benign according to our data. Variant chr13-110194880-G-T is described in ClinVar as Benign. ClinVar VariationId is 1248072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375820.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A1	NM_001845.6	MANE Select	c.1381+143C>A		intron	N/A	NP_001836.3
	COL4A1	NM_001303110.2		c.1381+143C>A		intron	N/A	NP_001290039.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A1	ENST00000375820.10	TSL:1 MANE Select	c.1381+143C>A		intron	N/A	ENSP00000364979.4
	COL4A1	ENST00000543140.6	TSL:1	c.1381+143C>A		intron	N/A	ENSP00000443348.1
	COL4A1	ENST00000650424.2		c.1381+143C>A		intron	N/A	ENSP00000497477.2

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110280 AN: 151862 Hom.: 40118 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.742

GnomAD4 exome AF: 0.751 AC: 421805 AN: 562026 Hom.: 159223 AF XY: 0.756 AC XY: 227966 AN XY: 301670

African (AFR) AF: 0.679 AC: 10159 AN: 14972

American (AMR) AF: 0.679 AC: 21746 AN: 32044

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 15611 AN: 19312

East Asian (EAS) AF: 0.627 AC: 19942 AN: 31804

South Asian (SAS) AF: 0.815 AC: 48896 AN: 60004

European-Finnish (FIN) AF: 0.759 AC: 33956 AN: 44732

Middle Eastern (MID) AF: 0.820 AC: 2662 AN: 3246

European-Non Finnish (NFE) AF: 0.755 AC: 245969 AN: 325702

Other (OTH) AF: 0.757 AC: 22864 AN: 30210

GnomAD4 genome AF: 0.726 AC: 110355 AN: 151980 Hom.: 40142 Cov.: 31 AF XY: 0.726 AC XY: 53920 AN XY: 74262

African (AFR) AF: 0.678 AC: 28115 AN: 41444

American (AMR) AF: 0.729 AC: 11133 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2756 AN: 3468

East Asian (EAS) AF: 0.615 AC: 3181 AN: 5170

South Asian (SAS) AF: 0.806 AC: 3871 AN: 4800

European-Finnish (FIN) AF: 0.757 AC: 7998 AN: 10572

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51033 AN: 67948

Other (OTH) AF: 0.743 AC: 1567 AN: 2108

Alfa AF: 0.722 Hom.: 6582

Bravo AF: 0.717

Asia WGS AF: 0.743 AC: 2585 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0020
DANN	Benign	0.47
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs505050; hg19: chr13-110847227;