X-108583309-A-G

Position:

• chrX-108583309-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_033380.3(COL4A5):​c.990+372A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 111,112 control chromosomes in the GnomAD database, including 2,816 homozygotes. There are 8,194 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.25 (2816 hom., 8194 hem., cov: 23)
• Consequence: COL4A5 NM_033380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

Genes affected

COL4A5 (HGNC:2207): (collagen type IV alpha 5 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Mutations in this gene are associated with X-linked Alport syndrome, also known as hereditary nephritis. 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. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-108583309-A-G is Benign according to our data. Variant chrX-108583309-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A5	NM_033380.3	c.990+372A>G		intron_variant		ENST00000328300.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A5	ENST00000328300.11	c.990+372A>G		intron_variant		1	NM_033380.3
COL4A5	ENST00000483338.1	c.-187+372A>G		intron_variant		1
COL4A5	ENST00000361603.7	c.990+372A>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 27405 AN: 111057 Hom.: 2813 Cov.: 23 AF XY: 0.245 AC XY: 8162 AN XY: 33347

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.247 AC: 27438 AN: 111112 Hom.: 2816 Cov.: 23 AF XY: 0.245 AC XY: 8194 AN XY: 33412

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.242

Alfa AF: 0.221 Hom.: 1361

Bravo AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.50

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: rs10521520; hg19: chrX-107826539;