X-108463618-C-A

Position:

• chrX-108463618-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant X-108463618-C-A is Benign according to our data. Variant chrX-108463618-C-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.81+23412C>A		intron_variant		ENST00000328300.11	NP_203699.1
COL4A5	NM_000495.5	c.81+23412C>A		intron_variant			NP_000486.1
COL4A5	XM_047441810.1	c.-296+23412C>A		intron_variant			XP_047297766.1
COL4A5	XM_047441811.1	c.81+23412C>A		intron_variant			XP_047297767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.81+23412C>A		intron_variant		1	NM_033380.3	ENSP00000331902
COL4A5	ENST00000361603.7	c.81+23412C>A		intron_variant		2		ENSP00000354505	P1
COL4A5	ENST00000470339.1	n.265+23412C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.751 AC: 82942 AN: 110423 Hom.: 22584 Cov.: 22 AF XY: 0.743 AC XY: 24245 AN XY: 32647

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

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.855

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.749

Alfa AF: 0.778 Hom.: 39655

Bravo AF: 0.728

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.30

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: rs5929099; hg19: chrX-107706848;