rs12049756

Positions:

• chr10-60110911-G-A

Variant summary

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

The ENST00000280772.7(ANK3):​c.2949-1857C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,124 control chromosomes in the GnomAD database, including 3,353 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 (3353 hom., cov: 32)
• Consequence: ANK3 ENST00000280772.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

Genes affected

ANK3 (HGNC:494): (ankyrin 3) Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_020987.5	c.2949-1857C>T		intron_variant		ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.2949-1857C>T		intron_variant		1	NM_020987.5	ENSP00000280772

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29437 AN: 152006 Hom.: 3351 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.194 AC: 29454 AN: 152124 Hom.: 3353 Cov.: 32 AF XY: 0.200 AC XY: 14844 AN XY: 74366

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.178

Alfa AF: 0.150 Hom.: 3267

Bravo AF: 0.201

Asia WGS AF: 0.306 AC: 1062 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.55

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: rs12049756; hg19: chr10-61870669;