X-108586590-A-AT

Position:

• chrX-108586590-A-AT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_033380.3(COL4A5):​c.1033-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,048,343 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., 4 hem., cov: 21)
  • Exomes 𝑓: 0.0030 (0 hom. 11 hem.)
• Consequence: COL4A5 NM_033380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

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 -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.1033-15dupT		intron_variant		ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.1033-15dupT		intron_variant		1	NM_033380.3	ENSP00000331902.7
COL4A5	ENST00000483338.1	c.-144-15dupT		intron_variant		1		ENSP00000495685.1
COL4A5	ENST00000361603.7	c.1033-15dupT		intron_variant		2		ENSP00000354505.2

Frequencies

GnomAD3 genomes AF: 0.000179 AC: 19 AN: 106333 Hom.: 0 Cov.: 21 AF XY: 0.000133 AC XY: 4 AN XY: 30093

Gnomad AFR AF: 0.000102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000910

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000979

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00300 AC: 2822 AN: 941977 Hom.: 0 Cov.: 26 AF XY: 0.0000369 AC XY: 11 AN XY: 298069

Gnomad4 AFR exome AF: 0.00367

Gnomad4 AMR exome AF: 0.00177

Gnomad4 ASJ exome AF: 0.00208

Gnomad4 EAS exome AF: 0.00172

Gnomad4 SAS exome AF: 0.00156

Gnomad4 FIN exome AF: 0.00104

Gnomad4 NFE exome AF: 0.00331

Gnomad4 OTH exome AF: 0.00270

GnomAD4 genome AF: 0.000179 AC: 19 AN: 106366 Hom.: 0 Cov.: 21 AF XY: 0.000133 AC XY: 4 AN XY: 30140

Gnomad4 AFR AF: 0.000102

Gnomad4 AMR AF: 0.000909

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000979

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
La Branchor		0.71
BranchPoint Hunter		6.0

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: rs104886089; hg19: chrX-107829820;