rs1837949

Positions:

• chr10-60685064-T-C
• chr10-60685064-T-G

Variant summary

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

The NM_001204403.2(ANK3):​c.57+48199A>G variant causes a intron change. The variant allele was found at a frequency of 0.319 in 1,335,330 control chromosomes in the GnomAD database, including 73,545 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 0.27 (6639 hom., cov: 33)
  • Exomes 𝑓: 0.33 (66906 hom.)
• Consequence: ANK3 NM_001204403.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00

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]

ARL4AP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_001204403.2	c.57+48199A>G		intron_variant			NP_001191332.1
ARL4AP1		n.60685064T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000373827.6	c.57+48199A>G		intron_variant		1		ENSP00000362933.2
ARL4AP1	ENST00000503220.1	n.560T>C		non_coding_transcript_exon_variant	1/1	6
ANK3	ENST00000510382.1	n.62+48199A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40936 AN: 152004 Hom.: 6638 Cov.: 33

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.326 AC: 385600 AN: 1183208 Hom.: 66906 Cov.: 16 AF XY: 0.331 AC XY: 197790 AN XY: 597762

Gnomad4 AFR exome AF: 0.0775

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.398

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.269 AC: 40959 AN: 152122 Hom.: 6639 Cov.: 33 AF XY: 0.279 AC XY: 20776 AN XY: 74364

Gnomad4 AFR AF: 0.0921

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.258

Alfa AF: 0.282 Hom.: 2201

Bravo AF: 0.260

Asia WGS AF: 0.414 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.63

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1837949; hg19: chr10-62444822; COSMIC: COSV65756587;