rs617111

Variant names:

• chr13-110155429-C-G
• rs617111
• NM_001845.6:c.4641-32G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-110155429-C-G
• chr13-110155429-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001845.6(COL4A1):​c.4641-32G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000514 in 1,555,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001845.6. 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.4641-32G>C		intron	N/A	NP_001836.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A1	ENST00000375820.10	TSL:1 MANE Select	c.4641-32G>C		intron	N/A	ENSP00000364979.4
	COL4A1	ENST00000650424.2		c.4641-32G>C		intron	N/A	ENSP00000497477.2
	COL4A1	ENST00000615732.3	TSL:5	c.4449-32G>C		intron	N/A	ENSP00000478222.3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000836 AC: 2 AN: 239142 AF XY: 0.00000773

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1402774 Hom.: 0 Cov.: 23 AF XY: 0.00000143 AC XY: 1 AN XY: 700594

African (AFR) AF: 0.00 AC: 0 AN: 32266

American (AMR) AF: 0.00 AC: 0 AN: 43990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25688

East Asian (EAS) AF: 0.0000765 AC: 3 AN: 39196

South Asian (SAS) AF: 0.00 AC: 0 AN: 84488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1060360

Other (OTH) AF: 0.00 AC: 0 AN: 58276

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152278 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 190

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0050
DANN	Benign	0.36
PhyloP100		-1.9

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: rs617111; hg19: chr13-110807776;