rs4308887

Variant names:

• chrX-108597204-A-G
• rs4308887
• NM_033380.3:c.1587+136A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-108597204-A-G
• chrX-108597204-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033380.3(COL4A5):​c.1587+136A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 740,527 control chromosomes in the GnomAD database, including 17,928 homozygotes. There are 53,617 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2071 hom., 6494 hem., cov: 22)
  • Exomes 𝑓: 0.24 (15857 hom. 47123 hem.)
• Consequence: COL4A5 NM_033380.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.686
• Publications: 5 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: G2P, ClinGen
• X-linked Alport syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-108597204-A-G is Benign according to our data. Variant chrX-108597204-A-G is described in ClinVar as Benign. ClinVar VariationId is 1177027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A5	NM_033380.3	MANE Select	c.1587+136A>G		intron	N/A	NP_203699.1	P29400-2
	COL4A5	NM_000495.5		c.1587+136A>G		intron	N/A	NP_000486.1	P29400-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A5	ENST00000328300.11	TSL:1 MANE Select	c.1587+136A>G		intron	N/A	ENSP00000331902.7	P29400-2
	COL4A5	ENST00000483338.1	TSL:1	c.411+136A>G		intron	N/A	ENSP00000495685.1	Q49AM6
	COL4A5	ENST00000949143.1		c.1587+136A>G		intron	N/A	ENSP00000619202.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 21478 AN: 110359 Hom.: 2071 Cov.: 22

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.241 AC: 152046 AN: 630114 Hom.: 15857 AF XY: 0.273 AC XY: 47123 AN XY: 172856

African (AFR) AF: 0.0629 AC: 1032 AN: 16407

American (AMR) AF: 0.568 AC: 15138 AN: 26629

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 2696 AN: 15315

East Asian (EAS) AF: 0.649 AC: 16345 AN: 25192

South Asian (SAS) AF: 0.382 AC: 14856 AN: 38900

European-Finnish (FIN) AF: 0.145 AC: 5377 AN: 36984

Middle Eastern (MID) AF: 0.199 AC: 403 AN: 2023

European-Non Finnish (NFE) AF: 0.203 AC: 89093 AN: 438327

Other (OTH) AF: 0.234 AC: 7106 AN: 30337

GnomAD4 genome AF: 0.195 AC: 21490 AN: 110413 Hom.: 2071 Cov.: 22 AF XY: 0.198 AC XY: 6494 AN XY: 32745

African (AFR) AF: 0.0641 AC: 1954 AN: 30503

American (AMR) AF: 0.439 AC: 4550 AN: 10356

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 443 AN: 2622

East Asian (EAS) AF: 0.572 AC: 2003 AN: 3499

South Asian (SAS) AF: 0.363 AC: 917 AN: 2528

European-Finnish (FIN) AF: 0.133 AC: 771 AN: 5808

Middle Eastern (MID) AF: 0.190 AC: 41 AN: 216

European-Non Finnish (NFE) AF: 0.195 AC: 10269 AN: 52710

Other (OTH) AF: 0.221 AC: 332 AN: 1503

Alfa AF: 0.171 Hom.: 1287

Bravo AF: 0.215

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	X-linked Alport syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		0.69
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: rs4308887; hg19: chrX-107840434;