rs1837950

Variant names:

• chr10-60685207-T-C
• rs1837950
• ENST00000373827.6:c.57+48056A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARL4AP1		n.60685207T>C		intragenic_variant
ANK3	NM_001204403.2	c.57+48056A>G		intron_variant	Intron 1 of 43		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000373827.6	c.57+48056A>G		intron_variant	Intron 1 of 43	1		ENSP00000362933.2
ARL4AP1	ENST00000503220.1	n.703T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1	6
ANK3	ENST00000510382.1	n.62+48056A>G		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.599 AC: 3109 AN: 5194

American (AMR) AF: 0.699 AC: 5041 AN: 7208

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 4077 AN: 5182

East Asian (EAS) AF: 0.577 AC: 4960 AN: 8592

South Asian (SAS) AF: 0.835 AC: 26495 AN: 31714

European-Finnish (FIN) AF: 0.682 AC: 16627 AN: 24382

Middle Eastern (MID) AF: 0.756 AC: 667 AN: 882

European-Non Finnish (NFE) AF: 0.679 AC: 83123 AN: 122374

Other (OTH) AF: 0.688 AC: 7525 AN: 10936

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

African (AFR) AF: 0.607 AC: 25185 AN: 41470

American (AMR) AF: 0.706 AC: 10799 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2755 AN: 3470

East Asian (EAS) AF: 0.567 AC: 2932 AN: 5172

South Asian (SAS) AF: 0.830 AC: 3996 AN: 4814

European-Finnish (FIN) AF: 0.700 AC: 7400 AN: 10578

Middle Eastern (MID) AF: 0.671 AC: 196 AN: 292

European-Non Finnish (NFE) AF: 0.686 AC: 46648 AN: 67988

Other (OTH) AF: 0.677 AC: 1429 AN: 2112

Alfa AF: 0.686 Hom.: 36971

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
PhyloP100		-0.0080
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1837950; hg19: chr10-62444965;