chr6-124748401-T-C

Variant names:

• chr6-124748401-T-C
• rs945949
• NM_001040214.3:c.475-42938T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040214.3(NKAIN2):​c.475-42938T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,746 control chromosomes in the GnomAD database, including 14,259 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 0.42 (14259 hom., cov: 32)
• Consequence: NKAIN2 NM_001040214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKAIN2	NM_001040214.3	MANE Select	c.475-42938T>C		intron	N/A	NP_001035304.1	Q5VXU1-1
	NKAIN2	NM_001300737.2		c.472-42938T>C		intron	N/A	NP_001287666.1	Q5VXU1-3
	NKAIN2	NM_153355.5		c.274-42938T>C		intron	N/A	NP_699186.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKAIN2	ENST00000368417.6	TSL:5 MANE Select	c.475-42938T>C		intron	N/A	ENSP00000357402.1	Q5VXU1-1
	RNF217-AS1	ENST00000655205.1		n.919+38059A>G		intron	N/A
	RNF217-AS1	ENST00000658682.1		n.748-3929A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64130 AN: 151628 Hom.: 14261 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.423 AC: 64160 AN: 151746 Hom.: 14259 Cov.: 32 AF XY: 0.413 AC XY: 30640 AN XY: 74158

African (AFR) AF: 0.329 AC: 13649 AN: 41424

American (AMR) AF: 0.351 AC: 5353 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1827 AN: 3466

East Asian (EAS) AF: 0.282 AC: 1435 AN: 5086

South Asian (SAS) AF: 0.419 AC: 2015 AN: 4814

European-Finnish (FIN) AF: 0.359 AC: 3797 AN: 10572

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34534 AN: 67834

Other (OTH) AF: 0.437 AC: 923 AN: 2112

Alfa AF: 0.476 Hom.: 10998

Bravo AF: 0.419

Asia WGS AF: 0.338 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.57
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs945949; hg19: chr6-125069547; COSMIC: COSV63702625;