rs41275106

Variant names:

• chr13-110242803-A-G
• rs41275106
• NM_001845.6:c.85-69T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-110242803-A-G
• chr13-110242803-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0200
• 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: Genomics England PanelApp, Orphanet, Ambry Genetics, G2P, PanelApp Australia
• autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, 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=-0.91).
• BP6: Variant 13-110242803-A-G is Benign according to our data. Variant chr13-110242803-A-G is described in ClinVar as Benign. ClinVar VariationId is 1242718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A1	NM_001845.6	MANE Select	c.85-69T>C		intron	N/A	NP_001836.3	P02462-1
	COL4A1	NM_001303110.2		c.85-69T>C		intron	N/A	NP_001290039.1	P02462-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A1	ENST00000375820.10	TSL:1 MANE Select	c.85-69T>C		intron	N/A	ENSP00000364979.4	P02462-1
	COL4A1	ENST00000543140.6	TSL:1	c.85-69T>C		intron	N/A	ENSP00000443348.1	P02462-2
	COL4A1	ENST00000650424.2		c.85-69T>C		intron	N/A	ENSP00000497477.2	A0A3B3ISV3

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

African (AFR) AF: 0.202 AC: 6362 AN: 31520

American (AMR) AF: 0.0694 AC: 3094 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3416 AN: 25638

East Asian (EAS) AF: 0.00536 AC: 211 AN: 39382

South Asian (SAS) AF: 0.184 AC: 15571 AN: 84546

European-Finnish (FIN) AF: 0.134 AC: 6869 AN: 51328

Middle Eastern (MID) AF: 0.180 AC: 1012 AN: 5624

European-Non Finnish (NFE) AF: 0.174 AC: 179918 AN: 1033684

Other (OTH) AF: 0.162 AC: 9268 AN: 57378

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

African (AFR) AF: 0.199 AC: 8245 AN: 41532

American (AMR) AF: 0.102 AC: 1551 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3468

East Asian (EAS) AF: 0.00789 AC: 41 AN: 5196

South Asian (SAS) AF: 0.172 AC: 831 AN: 4826

European-Finnish (FIN) AF: 0.121 AC: 1283 AN: 10600

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12038 AN: 68014

Other (OTH) AF: 0.151 AC: 320 AN: 2116

Alfa AF: 0.163 Hom.: 271

Bravo AF: 0.163

Asia WGS AF: 0.0930 AC: 327 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	-0.91
CADD	Benign	1.3
DANN	Benign	0.26
PhyloP100		0.020
PromoterAI		0.030	Neutral
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: rs41275106; hg19: chr13-110895150;