13-110206969-GAAA-GAAAAA

Position:

• chr13-110206969-GAAA-GAAAAA

Variant summary

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

The NM_001845.6(COL4A1):​c.781-80_781-79dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000478 in 1,154,738 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 0.0000071 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: COL4A1 NM_001845.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000543 (551/1014522) while in subpopulation AFR AF= 0.00139 (31/22268). AF 95% confidence interval is 0.00101. There are 0 homozygotes in gnomad4_exome. There are 293 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 551 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A1	NM_001845.6	c.781-80_781-79dupTT		intron_variant		ENST00000375820.10	NP_001836.3
COL4A1	NM_001303110.2	c.781-80_781-79dupTT		intron_variant			NP_001290039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A1	ENST00000375820.10	c.781-80_781-79dupTT		intron_variant		1	NM_001845.6	ENSP00000364979.4

Frequencies

GnomAD3 genomes AF: 0.00000713 AC: 1 AN: 140216 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.0000264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000543 AC: 551 AN: 1014522 Hom.: 0 AF XY: 0.000569 AC XY: 293 AN XY: 515176

Gnomad4 AFR exome AF: 0.00139

Gnomad4 AMR exome AF: 0.000386

Gnomad4 ASJ exome AF: 0.000706

Gnomad4 EAS exome AF: 0.000288

Gnomad4 SAS exome AF: 0.000536

Gnomad4 FIN exome AF: 0.000176

Gnomad4 NFE exome AF: 0.000574

Gnomad4 OTH exome AF: 0.000230

GnomAD4 genome AF: 0.00000713 AC: 1 AN: 140216 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 67944

Gnomad4 AFR AF: 0.0000264

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;