rs3818253

Variant names:

• chr20-35009073-G-A
• rs3818253
• NM_015638.3:c.1512-326C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015638.3(TRPC4AP):​c.1512-326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,142 control chromosomes in the GnomAD database, including 2,788 homozygotes. 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 0.19 (2788 hom., cov: 32)
• Consequence: TRPC4AP NM_015638.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

Genes affected

TRPC4AP (HGNC:16181): (transient receptor potential cation channel subfamily C member 4 associated protein) Enables phosphatase binding activity and ubiquitin ligase-substrate adaptor activity. Involved in protein ubiquitination and ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Part of Cul4A-RING E3 ubiquitin ligase complex. Is active in Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC4AP	NM_015638.3	c.1512-326C>T		intron_variant	Intron 12 of 18	ENST00000252015.3	NP_056453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC4AP	ENST00000252015.3	c.1512-326C>T		intron_variant	Intron 12 of 18	1	NM_015638.3	ENSP00000252015.2
TRPC4AP	ENST00000451813.6	c.1488-326C>T		intron_variant	Intron 12 of 18	2		ENSP00000400614.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28697 AN: 152024 Hom.: 2787 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.189 AC: 28701 AN: 152142 Hom.: 2788 Cov.: 32 AF XY: 0.189 AC XY: 14055 AN XY: 74358

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.203

Alfa AF: 0.187 Hom.: 482

Bravo AF: 0.185

Asia WGS AF: 0.212 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs3818253; hg19: chr20-33596876;