NM_033380.3:c.-16C>G

Variant names:

• chrX-108440110-C-G
• rs372416097
• NM_033380.3:c.-16C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033380.3(COL4A5):​c.-16C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 1,082,489 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: not found (cov: 21)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: COL4A5 NM_033380.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

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.-16C>G		5_prime_UTR	Exon 1 of 53	NP_203699.1	P29400-2
	COL4A5	NM_000495.5		c.-16C>G		5_prime_UTR	Exon 1 of 51	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.-16C>G		5_prime_UTR	Exon 1 of 53	ENSP00000331902.7	P29400-2
	COL4A5	ENST00000477429.1	TSL:1	n.267C>G		non_coding_transcript_exon	Exon 1 of 2
	COL4A5	ENST00000949143.1		c.-16C>G		5_prime_UTR	Exon 1 of 51	ENSP00000619202.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000565 AC: 1 AN: 176879 AF XY: 0.0000161

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1082489 Hom.: 0 Cov.: 28 AF XY: 0.00000286 AC XY: 1 AN XY: 349819

African (AFR) AF: 0.00 AC: 0 AN: 26103

American (AMR) AF: 0.00 AC: 0 AN: 35055

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19270

East Asian (EAS) AF: 0.00 AC: 0 AN: 30126

South Asian (SAS) AF: 0.00 AC: 0 AN: 53290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40197

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4057

European-Non Finnish (NFE) AF: 0.00000241 AC: 2 AN: 828790

Other (OTH) AF: 0.00 AC: 0 AN: 45601

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.92
PhyloP100		1.1
PromoterAI		-0.050	Neutral

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: rs372416097; hg19: chrX-107683340;