rs5929126

chrX-108447766-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_033380.3(COL4A5):c.81+7560A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 111,867 control chromosomes in the GnomAD database, including 55 homozygotes. There are 881 hemizygotes in GnomAD. 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 0.027 (55 hom., 881 hem., cov: 23)
• Consequence: COL4A5 NM_033380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0274 (3062/111867) while in subpopulation NFE AF= 0.0436 (2313/53096). AF 95% confidence interval is 0.0421. There are 55 homozygotes in gnomad4. There are 881 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 55 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A5	NM_033380.3	c.81+7560A>C		intron_variant		ENST00000328300.11
COL4A5	NM_000495.5	c.81+7560A>C		intron_variant
COL4A5	XM_047441810.1	c.-296+7560A>C		intron_variant
COL4A5	XM_047441811.1	c.81+7560A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A5	ENST00000328300.11	c.81+7560A>C		intron_variant		1	NM_033380.3
COL4A5	ENST00000361603.7	c.81+7560A>C		intron_variant		2		P1
COL4A5	ENST00000642185.1	c.*122+7262A>C		intron_variant, NMD_transcript_variant
COL4A5	ENST00000470339.1	n.265+7560A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 3063 AN: 111814 Hom.: 55 Cov.: 23 AF XY: 0.0260 AC XY: 882 AN XY: 33980

Gnomad AFR AF: 0.00487

Gnomad AMI AF: 0.00881

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.000280

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.0436

Gnomad OTH AF: 0.0238

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

GnomAD4 genome AF: 0.0274 AC: 3062 AN: 111867 Hom.: 55 Cov.: 23 AF XY: 0.0259 AC XY: 881 AN XY: 34043

Gnomad4 AFR AF: 0.00486

Gnomad4 AMR AF: 0.0195

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.000281

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0379

Gnomad4 NFE AF: 0.0436

Gnomad4 OTH AF: 0.0235

Alfa AF: 0.0370 Hom.: 559

Bravo AF: 0.0255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.3
Dann	Benign	0.60

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: rs5929126; hg19: chrX-107690996;