NM_033380.3:c.81+8869C>T

Variant names:

• chrX-108449075-C-T
• rs5929098
• NM_033380.3:c.81+8869C>T

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+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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.81+8869C>T		intron_variant	Intron 1 of 52	ENST00000328300.11	NP_203699.1
COL4A5	NM_000495.5	c.81+8869C>T		intron_variant	Intron 1 of 50		NP_000486.1
COL4A5	XM_047441810.1	c.-296+8869C>T		intron_variant	Intron 1 of 53		XP_047297766.1
COL4A5	XM_047441811.1	c.81+8869C>T		intron_variant	Intron 1 of 41		XP_047297767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.81+8869C>T		intron_variant	Intron 1 of 52	1	NM_033380.3	ENSP00000331902.7
COL4A5	ENST00000361603.7	c.81+8869C>T		intron_variant	Intron 1 of 50	2		ENSP00000354505.2
COL4A5	ENST00000470339.1	n.265+8869C>T		intron_variant	Intron 1 of 5	3
COL4A5	ENST00000642185.1	n.*122+8571C>T		intron_variant	Intron 2 of 2			ENSP00000495101.1

Frequencies

GnomAD3 genomes AF: 0.752 AC: 82985 AN: 110316 Hom.: 22586 Cov.: 23

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

African (AFR) AF: 0.789 AC: 23912 AN: 30313

American (AMR) AF: 0.532 AC: 5483 AN: 10314

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2163 AN: 2625

East Asian (EAS) AF: 0.425 AC: 1478 AN: 3476

South Asian (SAS) AF: 0.611 AC: 1590 AN: 2601

European-Finnish (FIN) AF: 0.855 AC: 5006 AN: 5855

Middle Eastern (MID) AF: 0.785 AC: 168 AN: 214

European-Non Finnish (NFE) AF: 0.788 AC: 41633 AN: 52818

Other (OTH) AF: 0.754 AC: 1116 AN: 1480

Alfa AF: 0.763 Hom.: 36711

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
PhyloP100		0.58
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: rs5929098; hg19: chrX-107692305;