rs781484

Positions:

• chr6-124656509-G-A
• chr6-124656509-G-C

Variant summary

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

The NM_001040214.3(NKAIN2):​c.274-1677G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,688 control chromosomes in the GnomAD database, including 15,970 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 0.46 (15970 hom., cov: 30)
• Consequence: NKAIN2 NM_001040214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

Genes affected

NKAIN2 (HGNC:16443): (sodium/potassium transporting ATPase interacting 2) This gene encodes a transmembrane protein that interacts with the beta subunit of a sodium/potassium-transporting ATPase. A chromosomal translocation involving this gene is a cause of lymphoma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

RNF217-AS1 (HGNC:50866): (RNF217 antisense RNA 1 (head to head))

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKAIN2	NM_001040214.3	c.274-1677G>A		intron_variant		ENST00000368417.6	NP_001035304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKAIN2	ENST00000368417.6	c.274-1677G>A		intron_variant		5	NM_001040214.3	ENSP00000357402	P1
RNF217-AS1	ENST00000663792.1	n.759-7853C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69046 AN: 151572 Hom.: 15966 Cov.: 30

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.455 AC: 69091 AN: 151688 Hom.: 15970 Cov.: 30 AF XY: 0.452 AC XY: 33495 AN XY: 74068

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.478

Alfa AF: 0.490 Hom.: 14797

Bravo AF: 0.456

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.30
DANN	Benign	0.55

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: rs781484; hg19: chr6-124977655; COSMIC: COSV63687040;