rs1837950

Positions:

• chr10-60685207-T-C

Variant summary

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

The ENST00000373827.6(ANK3):​c.57+48056A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 368,556 control chromosomes in the GnomAD database, including 88,078 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 0.67 (34377 hom., cov: 32)
  • Exomes 𝑓: 0.70 (53701 hom.)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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:17741): (ADP ribosylation factor like GTPase 4A pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_001204403.2	c.57+48056A>G		intron_variant			NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000373827.6	c.57+48056A>G		intron_variant		1		ENSP00000362933
ARL4AP1	ENST00000503220.1	n.703T>C		non_coding_transcript_exon_variant	1/1
ANK3	ENST00000510382.1	n.62+48056A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101937 AN: 151974 Hom.: 34350 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.679

GnomAD4 exome AF: 0.700 AC: 151624 AN: 216464 Hom.: 53701 Cov.: 4 AF XY: 0.713 AC XY: 83041 AN XY: 116416

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.699

Gnomad4 ASJ exome AF: 0.787

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.835

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.671 AC: 102011 AN: 152092 Hom.: 34377 Cov.: 32 AF XY: 0.676 AC XY: 50277 AN XY: 74344

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.677

Alfa AF: 0.688 Hom.: 28086

Bravo AF: 0.665

Asia WGS AF: 0.708 AC: 2456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.0
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1837950; hg19: chr10-62444965;