rs3832900

Variant names:

• chr13-110211627-CAAAAT-C
• rs3832900
• NM_001845.6:c.468+15_468+19delATTTT

Your query was ambiguous. Multiple possible variants found:

• chr13-110211627-CAAAAT-C
• chr13-110211627-CAAAAT-CAAAATAAAAT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001845.6(COL4A1):​c.468+15_468+19delATTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,609,704 control chromosomes in the GnomAD database, including 1,293 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (306 hom., cov: 32)
  • Exomes 𝑓: 0.022 (987 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.06
• Publications: 3 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 -16 ACMG points.

• BP6: Variant 13-110211627-CAAAAT-C is Benign according to our data. Variant chr13-110211627-CAAAAT-C is described in ClinVar as [Benign]. Clinvar id is 258258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A1	NM_001845.6	c.468+15_468+19delATTTT		intron_variant	Intron 8 of 51	ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2	c.468+15_468+19delATTTT		intron_variant	Intron 8 of 24		NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10	c.468+15_468+19delATTTT		intron_variant	Intron 8 of 51	1	NM_001845.6	ENSP00000364979.4

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7157 AN: 152026 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0962

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.00520

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0411

GnomAD2 exomes AF: 0.0384 AC: 9526 AN: 248090 AF XY: 0.0324

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.0111

Gnomad EAS exome AF: 0.0953

Gnomad FIN exome AF: 0.00560

Gnomad NFE exome AF: 0.0150

Gnomad OTH exome AF: 0.0277

GnomAD4 exome AF: 0.0216 AC: 31492 AN: 1457560 Hom.: 987 AF XY: 0.0205 AC XY: 14868 AN XY: 725078

African (AFR) AF: 0.116 AC: 3867 AN: 33266

American (AMR) AF: 0.104 AC: 4587 AN: 44028

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 305 AN: 26036

East Asian (EAS) AF: 0.107 AC: 4248 AN: 39644

South Asian (SAS) AF: 0.00570 AC: 486 AN: 85278

European-Finnish (FIN) AF: 0.00608 AC: 322 AN: 52928

Middle Eastern (MID) AF: 0.0278 AC: 159 AN: 5728

European-Non Finnish (NFE) AF: 0.0144 AC: 15999 AN: 1110410

Other (OTH) AF: 0.0252 AC: 1519 AN: 60242

GnomAD4 genome AF: 0.0472 AC: 7175 AN: 152144 Hom.: 306 Cov.: 32 AF XY: 0.0459 AC XY: 3413 AN XY: 74402

African (AFR) AF: 0.109 AC: 4523 AN: 41470

American (AMR) AF: 0.0608 AC: 930 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.0970 AC: 503 AN: 5186

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4830

European-Finnish (FIN) AF: 0.00520 AC: 55 AN: 10574

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 982 AN: 68012

Other (OTH) AF: 0.0492 AC: 104 AN: 2112

Alfa AF: 0.0295 Hom.: 26

Bravo AF: 0.0580

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 28, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Brain small vessel disease 1 with or without ocular anomalies Benign:2

Jun 01, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Porencephalic cyst Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3832900; hg19: chr13-110863974; COSMIC: COSV107488356;