rs7917800

chr10-60080409-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.4432+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 769,518 control chromosomes in the GnomAD database, including 4,960 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 0.13 (1572 hom., cov: 32)
  • Exomes 𝑓: 0.094 (3388 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.4432+128G>A		intron_variant		ENST00000280772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.4432+128G>A		intron_variant		1	NM_020987.5

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19636 AN: 152044 Hom.: 1572 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0943 AC: 58246 AN: 617358 Hom.: 3388 AF XY: 0.0901 AC XY: 29364 AN XY: 325900

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.0687

Gnomad4 ASJ exome AF: 0.0653

Gnomad4 EAS exome AF: 0.000458

Gnomad4 SAS exome AF: 0.0202

Gnomad4 FIN exome AF: 0.0861

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.0987

GnomAD4 genome AF: 0.129 AC: 19655 AN: 152160 Hom.: 1572 Cov.: 32 AF XY: 0.123 AC XY: 9160 AN XY: 74388

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.0910

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0770

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.112

Alfa AF: 0.115 Hom.: 1133

Bravo AF: 0.135

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.53

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: rs7917800; hg19: chr10-61840167; COSMIC: COSV55065712; COSMIC: COSV55065712;