2-227132754-A-G

Position:

• chr2-227132754-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000092.5(COL4A4):​c.192+7407T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,896 control chromosomes in the GnomAD database, including 9,778 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9778 hom., cov: 31)
• Consequence: COL4A4 NM_000092.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

Genes affected

COL4A4 (HGNC:2206): (collagen type IV alpha 4 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset of basement membranes. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3' UTR. [provided by RefSeq, Jul 2008]

COL4A4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A4	NM_000092.5	c.192+7407T>C		intron_variant		ENST00000396625.5	NP_000083.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A4	ENST00000396625.5	c.192+7407T>C		intron_variant		5	NM_000092.5	ENSP00000379866.3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52878 AN: 151776 Hom.: 9780 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.333

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 52899 AN: 151896 Hom.: 9778 Cov.: 31 AF XY: 0.351 AC XY: 26041 AN XY: 74232

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.330

Alfa AF: 0.391 Hom.: 1513

Bravo AF: 0.330

Asia WGS AF: 0.274 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.42

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: rs1882432; hg19: chr2-227997470;