chr13-110182848-C-A

Variant names:

• chr13-110182848-C-A
• rs7329411
• NM_001845.6:c.2095+145G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001845.6(COL4A1):​c.2095+145G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 709,020 control chromosomes in the GnomAD database, including 47,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (11678 hom., cov: 34)
  • Exomes 𝑓: 0.36 (36227 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.243
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-110182848-C-A is Benign according to our data. Variant chr13-110182848-C-A is described in ClinVar as Benign. ClinVar VariationId is 1258367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 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.2095+145G>T		intron	N/A	NP_001836.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A1	ENST00000375820.10	TSL:1 MANE Select	c.2095+145G>T		intron	N/A	ENSP00000364979.4
	COL4A1	ENST00000650424.2		c.2095+145G>T		intron	N/A	ENSP00000497477.2
	COL4A1	ENST00000933608.1		c.2095+145G>T		intron	N/A	ENSP00000603667.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59247 AN: 152098 Hom.: 11662 Cov.: 34

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.357 AC: 198506 AN: 556804 Hom.: 36227 AF XY: 0.355 AC XY: 103678 AN XY: 292078

African (AFR) AF: 0.461 AC: 6588 AN: 14280

American (AMR) AF: 0.380 AC: 7771 AN: 20462

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 4604 AN: 15000

East Asian (EAS) AF: 0.382 AC: 12158 AN: 31846

South Asian (SAS) AF: 0.338 AC: 16614 AN: 49108

European-Finnish (FIN) AF: 0.343 AC: 11309 AN: 32952

Middle Eastern (MID) AF: 0.263 AC: 587 AN: 2232

European-Non Finnish (NFE) AF: 0.355 AC: 128123 AN: 361186

Other (OTH) AF: 0.362 AC: 10752 AN: 29738

GnomAD4 genome AF: 0.390 AC: 59314 AN: 152216 Hom.: 11678 Cov.: 34 AF XY: 0.387 AC XY: 28815 AN XY: 74414

African (AFR) AF: 0.457 AC: 18981 AN: 41522

American (AMR) AF: 0.375 AC: 5736 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3468

East Asian (EAS) AF: 0.414 AC: 2140 AN: 5166

South Asian (SAS) AF: 0.344 AC: 1663 AN: 4834

European-Finnish (FIN) AF: 0.340 AC: 3596 AN: 10592

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24604 AN: 68018

Other (OTH) AF: 0.384 AC: 812 AN: 2112

Alfa AF: 0.382 Hom.: 1902

Bravo AF: 0.397

Asia WGS AF: 0.413 AC: 1433 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.89
DANN	Benign	0.52
PhyloP100		-0.24
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: rs7329411; hg19: chr13-110835195;