X-108449075-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_033380.3(COL4A5):c.81+8869C>T 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 (22583 hom., 24329 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: COL4A5 NM_033380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-108449075-C-T is Benign according to our data. Variant chrX-108449075-C-T is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd at 22586 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A5	NM_033380.3	c.81+8869C>T		intron_variant		ENST00000328300.11
COL4A5	NM_000495.5	c.81+8869C>T		intron_variant
COL4A5	XM_047441810.1	c.-296+8869C>T		intron_variant
COL4A5	XM_047441811.1	c.81+8869C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A5	ENST00000328300.11	c.81+8869C>T		intron_variant		1	NM_033380.3
COL4A5	ENST00000361603.7	c.81+8869C>T		intron_variant		2		P1
COL4A5	ENST00000642185.1	c.*122+8571C>T		intron_variant, NMD_transcript_variant
COL4A5	ENST00000470339.1	n.265+8869C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.752 AC: 82985 AN: 110316 Hom.: 22586 Cov.: 23 AF XY: 0.746 AC XY: 24292 AN XY: 32562

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.749

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: 0.752 AC: 83011 AN: 110366 Hom.: 22583 Cov.: 23 AF XY: 0.746 AC XY: 24329 AN XY: 32622

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.855

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.754

Alfa AF: 0.768 Hom.: 26251

Bravo AF: 0.728

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	5.8
Dann	Benign	0.72

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: rs5929098; hg19: chrX-107692305;