rs11814752

Positions:

• chr10-60194492-G-A

Variant summary

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

The NM_020987.5(ANK3):​c.1887+1653C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,234 control chromosomes in the GnomAD database, including 1,028 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 0.10 (1028 hom., cov: 33)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_020987.5	c.1887+1653C>T		intron_variant		ENST00000280772.7	NP_066267.2
ANK3	NM_001204403.2	c.1869+1653C>T		intron_variant			NP_001191332.1
ANK3	NM_001204404.2	c.1836+1653C>T		intron_variant			NP_001191333.1
ANK3	NM_001320874.2	c.1887+1653C>T		intron_variant			NP_001307803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.1887+1653C>T		intron_variant		1	NM_020987.5	ENSP00000280772

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15737 AN: 152118 Hom.: 1027 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.104 AC: 15763 AN: 152234 Hom.: 1028 Cov.: 33 AF XY: 0.101 AC XY: 7529 AN XY: 74448

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0723

Gnomad4 ASJ AF: 0.0779

Gnomad4 EAS AF: 0.0650

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0519

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0893 Hom.: 357

Bravo AF: 0.106

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.25

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: rs11814752; hg19: chr10-61954250;