rs4948410

Positions:

• chr10-60356289-G-A
• chr10-60356289-G-C
• chr10-60356289-G-T

Variant summary

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

The NM_020987.5(ANK3):​c.114+33136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,168 control chromosomes in the GnomAD database, including 40,810 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 0.73 (40810 hom., cov: 33)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_020987.5	c.114+33136C>T		intron_variant		ENST00000280772.7	NP_066267.2
ANK3	NM_001204403.2	c.97-76650C>T		intron_variant			NP_001191332.1
ANK3	NM_001204404.2	c.64-76650C>T		intron_variant			NP_001191333.1
ANK3	NM_001320874.2	c.114+33136C>T		intron_variant			NP_001307803.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.114+33136C>T		intron_variant		1	NM_020987.5	ENSP00000280772

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110652 AN: 152050 Hom.: 40777 Cov.: 33

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.728 AC: 110729 AN: 152168 Hom.: 40810 Cov.: 33 AF XY: 0.734 AC XY: 54619 AN XY: 74404

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.746

Alfa AF: 0.771 Hom.: 24099

Bravo AF: 0.716

Asia WGS AF: 0.801 AC: 2785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.23

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: rs4948410; hg19: chr10-62116047;