rs5929126

Variant names:

• chrX-108447766-A-C
• rs5929126
• NM_033380.3:c.81+7560A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000328300.11(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 ENST00000328300.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 2 publications found

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]

COL4A5 Gene-Disease associations (from GenCC):

• Alport syndrome

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen, G2P
• X-linked Alport syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 55 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000328300.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A5	NM_033380.3	MANE Select	c.81+7560A>C		intron	N/A	NP_203699.1
	COL4A5	NM_000495.5		c.81+7560A>C		intron	N/A	NP_000486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A5	ENST00000328300.11	TSL:1 MANE Select	c.81+7560A>C		intron	N/A	ENSP00000331902.7
	COL4A5	ENST00000361603.7	TSL:2	c.81+7560A>C		intron	N/A	ENSP00000354505.2
	COL4A5	ENST00000470339.1	TSL:3	n.265+7560A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 3063 AN: 111814 Hom.: 55 Cov.: 23

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

African (AFR) AF: 0.00486 AC: 150 AN: 30876

American (AMR) AF: 0.0195 AC: 206 AN: 10550

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 117 AN: 2637

East Asian (EAS) AF: 0.000281 AC: 1 AN: 3564

South Asian (SAS) AF: 0.00 AC: 0 AN: 2644

European-Finnish (FIN) AF: 0.0379 AC: 230 AN: 6070

Middle Eastern (MID) AF: 0.0138 AC: 3 AN: 217

European-Non Finnish (NFE) AF: 0.0436 AC: 2313 AN: 53096

Other (OTH) AF: 0.0235 AC: 36 AN: 1532

Alfa AF: 0.0349 Hom.: 820

Bravo AF: 0.0255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.60
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5929126; hg19: chrX-107690996;