rs4308887

chrX-108597204-A-GchrX-108597204-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033380.3(COL4A5):c.1587+136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 740,527 control chromosomes in the GnomAD database, including 17,928 homozygotes. There are 53,617 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2071 hom., 6494 hem., cov: 22)
  • Exomes 𝑓: 0.24 (15857 hom. 47123 hem.)
• Consequence: COL4A5 NM_033380.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.686

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-108597204-A-G is Benign according to our data. Variant chrX-108597204-A-G is described in ClinVar as [Benign]. Clinvar id is 1177027.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-108597204-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A5	NM_033380.3	c.1587+136A>G		intron_variant		ENST00000328300.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A5	ENST00000328300.11	c.1587+136A>G		intron_variant		1	NM_033380.3
COL4A5	ENST00000483338.1	c.411+136A>G		intron_variant		1
COL4A5	ENST00000361603.7	c.1587+136A>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 21478 AN: 110359 Hom.: 2071 Cov.: 22 AF XY: 0.198 AC XY: 6479 AN XY: 32681

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.241 AC: 152046 AN: 630114 Hom.: 15857 AF XY: 0.273 AC XY: 47123 AN XY: 172856

Gnomad4 AFR exome AF: 0.0629

Gnomad4 AMR exome AF: 0.568

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.649

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.195 AC: 21490 AN: 110413 Hom.: 2071 Cov.: 22 AF XY: 0.198 AC XY: 6494 AN XY: 32745

Gnomad4 AFR AF: 0.0641

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.221

Alfa AF: 0.171 Hom.: 1287

Bravo AF: 0.215

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

X-linked Alport syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.6
Dann	Benign	0.65

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: rs4308887; hg19: chrX-107840434;