rs7329411

chr13-110182848-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.2095+145G>T		intron_variant		ENST00000375820.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.2095+145G>T		intron_variant		1	NM_001845.6	P1
COL4A1	ENST00000649738.1	n.2225+145G>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.380

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.362

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

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.384

Alfa AF: 0.379 Hom.: 1817

Bravo AF: 0.397

Asia WGS AF: 0.413 AC: 1433 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.89
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs7329411; hg19: chr13-110835195;