13-110206969-GAA-G

Position:

• chr13-110206969-GAA-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001845.6(COL4A1):​c.781-80_781-79del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,159,466 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00050 (0 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000328 (46/140280) while in subpopulation AFR AF= 0.000894 (34/38020). AF 95% confidence interval is 0.000657. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A1	NM_001845.6	c.781-80_781-79del		intron_variant		ENST00000375820.10
COL4A1	NM_001303110.2	c.781-80_781-79del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A1	ENST00000375820.10	c.781-80_781-79del		intron_variant		1	NM_001845.6	P1

Frequencies

GnomAD3 genomes AF: 0.000328 AC: 46 AN: 140218 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.000896

Gnomad AMI AF: 0.00118

Gnomad AMR AF: 0.000354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000227

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000783

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000496 AC: 506 AN: 1019186 Hom.: 0 AF XY: 0.000508 AC XY: 263 AN XY: 517596

Gnomad4 AFR exome AF: 0.00165

Gnomad4 AMR exome AF: 0.000911

Gnomad4 ASJ exome AF: 0.000300

Gnomad4 EAS exome AF: 0.0000634

Gnomad4 SAS exome AF: 0.000198

Gnomad4 FIN exome AF: 0.000440

Gnomad4 NFE exome AF: 0.000506

Gnomad4 OTH exome AF: 0.000412

GnomAD4 genome AF: 0.000328 AC: 46 AN: 140280 Hom.: 0 Cov.: 18 AF XY: 0.000323 AC XY: 22 AN XY: 68032

Gnomad4 AFR AF: 0.000894

Gnomad4 AMR AF: 0.000354

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000228

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000783

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs60585275; hg19: chr13-110859316;