rs4948256

chr10-60197154-C-Achr10-60197154-C-Gchr10-60197154-C-T

Variant summary

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

The NM_020987.5(ANK3):c.1690-529G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,194 control chromosomes in the GnomAD database, including 3,277 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 (3277 hom., cov: 32)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.1690-529G>T		intron_variant		ENST00000280772.7
ANK3	NM_001204403.2	c.1672-529G>T		intron_variant
ANK3	NM_001204404.2	c.1639-529G>T		intron_variant
ANK3	NM_001320874.2	c.1690-529G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.1690-529G>T		intron_variant		1	NM_020987.5

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28288 AN: 152076 Hom.: 3283 Cov.: 32

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.186 AC: 28269 AN: 152194 Hom.: 3277 Cov.: 32 AF XY: 0.190 AC XY: 14105 AN XY: 74398

Gnomad4 AFR AF: 0.0584

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.203

Alfa AF: 0.213 Hom.: 4820

Bravo AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.7
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4948256; hg19: chr10-61956912;