rs4924445

chr15-40281212-G-A

Variant summary

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

The NM_001190479.3(ANKRD63):c.*232C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,124 control chromosomes in the GnomAD database, including 9,421 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 0.34 (9421 hom., cov: 33)
• Consequence: ANKRD63 NM_001190479.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

Genes affected

ANKRD63 (HGNC:40027): (ankyrin repeat domain 63)

PLCB2 (HGNC:9055): (phospholipase C beta 2) The protein encoded by this gene is a phosphodiesterase that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. The encoded protein is activated by G proteins and has been shown to be involved in the type 2 taste receptor signal transduction pathway. In addition, nuclear factor kappa B can regulate the transcription of this gene, whose protein product is also an important regulator of platelet responses. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD63	NM_001190479.3	c.*232C>T		3_prime_UTR_variant	1/1	ENST00000434396.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD63	ENST00000434396.2	c.*232C>T		3_prime_UTR_variant	1/1		NM_001190479.3	P1
PLCB2	ENST00000560009.1	n.395-2868C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51046 AN: 152008 Hom.: 9417 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.336 AC: 51069 AN: 152124 Hom.: 9421 Cov.: 33 AF XY: 0.341 AC XY: 25332 AN XY: 74366

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.344

Alfa AF: 0.386 Hom.: 18618

Bravo AF: 0.332

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.0
Dann	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4924445; hg19: chr15-40573413;