rs4924445

Variant names:

• chr15-40281212-G-A
• rs4924445
• NM_001190479.3:c.*232C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190479.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD63	NM_001190479.3	MANE Select	c.*232C>T		3_prime_UTR	Exon 1 of 1	NP_001177408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD63	ENST00000434396.2	TSL:6 MANE Select	c.*232C>T		3_prime_UTR	Exon 1 of 1	ENSP00000399547.1
	PLCB2	ENST00000560009.1	TSL:4	n.395-2868C>T		intron	N/A

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

African (AFR) AF: 0.197 AC: 8185 AN: 41514

American (AMR) AF: 0.450 AC: 6874 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1544 AN: 3464

East Asian (EAS) AF: 0.136 AC: 705 AN: 5178

South Asian (SAS) AF: 0.482 AC: 2320 AN: 4812

European-Finnish (FIN) AF: 0.378 AC: 3997 AN: 10576

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26241 AN: 67980

Other (OTH) AF: 0.344 AC: 728 AN: 2116

Alfa AF: 0.374 Hom.: 30554

Bravo AF: 0.332

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.76
PhyloP100		0.087

Splicing

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

Other links and lift over

dbSNP: rs4924445; hg19: chr15-40573413;