rs7333204

Positions:

• chr13-110209324-T-C

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.651+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,379,242 control chromosomes in the GnomAD database, including 47,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5499 hom., cov: 32)
  • Exomes 𝑓: 0.25 (42066 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.422

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=-0.86).
• BP6: Variant 13-110209324-T-C is Benign according to our data. Variant chr13-110209324-T-C is described in ClinVar as [Benign]. Clinvar id is 1293042.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-110209324-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.651+68A>G		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2	c.651+68A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.651+68A>G		intron_variant		1	NM_001845.6	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40175 AN: 151768 Hom.: 5491 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.0619

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.253 AC: 310833 AN: 1227356 Hom.: 42066 AF XY: 0.253 AC XY: 157043 AN XY: 621300

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.0321

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.265 AC: 40219 AN: 151886 Hom.: 5499 Cov.: 32 AF XY: 0.266 AC XY: 19775 AN XY: 74240

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.228

Alfa AF: 0.276 Hom.: 763

Bravo AF: 0.262

Asia WGS AF: 0.133 AC: 465 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 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.43

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: rs7333204; hg19: chr13-110861671; COSMIC: COSV65423079;