18-9149439-A-T

Position:

• chr18-9149439-A-T

Variant summary

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

The NM_015208.5(ANKRD12):​c.-52+12474A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,038 control chromosomes in the GnomAD database, including 24,858 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 0.56 (24858 hom., cov: 32)
• Consequence: ANKRD12 NM_015208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569

Genes affected

ANKRD12 (HGNC:29135): (ankyrin repeat domain 12) This gene encodes a member of the ankyrin repeats-containing cofactor family. These proteins may inhibit the transcriptional activity of nuclear receptors through the recruitment of histone deacetylases. The encoded protein interacts with p160 coactivators and also represses transcription mediated by the coactivator alteration/deficiency in activation 3 (ADA3). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD12	NM_015208.5	c.-52+12474A>T		intron_variant		ENST00000262126.9	NP_056023.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD12	ENST00000262126.9	c.-52+12474A>T		intron_variant		1	NM_015208.5	ENSP00000262126	P4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84934 AN: 151920 Hom.: 24851 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.559 AC: 84970 AN: 152038 Hom.: 24858 Cov.: 32 AF XY: 0.566 AC XY: 42048 AN XY: 74310

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.592

Alfa AF: 0.579 Hom.: 3160

Bravo AF: 0.548

Asia WGS AF: 0.615 AC: 2126 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs4797356; hg19: chr18-9149437;