rs5929099

Variant names:

• chrX-108463618-C-A
• rs5929099
• NM_033380.3:c.81+23412C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033380.3(COL4A5):​c.81+23412C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.75 (22581 hom., 24287 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: COL4A5 NM_033380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033380.3. 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+23412C>A		intron	N/A	NP_203699.1
	COL4A5	NM_000495.5		c.81+23412C>A		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+23412C>A		intron	N/A	ENSP00000331902.7
	COL4A5	ENST00000361603.7	TSL:2	c.81+23412C>A		intron	N/A	ENSP00000354505.2
	COL4A5	ENST00000470339.1	TSL:3	n.265+23412C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.751 AC: 82942 AN: 110423 Hom.: 22584 Cov.: 22

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.789

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.744

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.751 AC: 82973 AN: 110479 Hom.: 22581 Cov.: 22 AF XY: 0.742 AC XY: 24287 AN XY: 32713

African (AFR) AF: 0.788 AC: 23906 AN: 30353

American (AMR) AF: 0.531 AC: 5523 AN: 10398

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2167 AN: 2634

East Asian (EAS) AF: 0.421 AC: 1469 AN: 3492

South Asian (SAS) AF: 0.619 AC: 1595 AN: 2575

European-Finnish (FIN) AF: 0.855 AC: 5019 AN: 5870

Middle Eastern (MID) AF: 0.778 AC: 168 AN: 216

European-Non Finnish (NFE) AF: 0.787 AC: 41545 AN: 52780

Other (OTH) AF: 0.749 AC: 1120 AN: 1495

Alfa AF: 0.771 Hom.: 51437

Bravo AF: 0.728

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		0.51
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: rs5929099; hg19: chrX-107706848;