chr11-117860724-G-C

Variant names:

• chr11-117860724-G-C
• rs1815774
• NM_022003.4:c.-6+15868C>G

Variant summary

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

The NM_022003.4(FXYD6):​c.-6+15868C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,132 control chromosomes in the GnomAD database, including 18,265 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 0.48 (18265 hom., cov: 33)
• Consequence: FXYD6 NM_022003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 6 publications found

Genes affected

FXYD6 (HGNC:4030): (FXYD domain containing ion transport regulator 6) This gene encodes a member of the FXYD family of transmembrane proteins. This particular protein encodes phosphohippolin, which likely affects the activity of Na,K-ATPase. Multiple alternatively spliced transcript variants encoding the same protein have been described. Related pseudogenes have been identified on chromosomes 10 and X. Read-through transcripts have been observed between this locus and the downstream sodium/potassium-transporting ATPase subunit gamma (FXYD2, GeneID 486) locus.[provided by RefSeq, Feb 2011]

FXYD6-FXYD2 (HGNC:39978): (FXYD6-FXYD2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring FXYD domain-containing ion transport regulator 6 (GeneID 53826) and sodium/potassium-transporting ATPase subunit gamma (GeneID 486) genes on chromosome 11. One read-through transcript produces a fusion protein that shares sequence identity with each individual gene product, while another read-through transcript encodes a protein that has a distinct C-terminus and only shares sequence identity with the upstream locus (GeneID 53826). [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022003.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6	NM_022003.4	MANE Select	c.-6+15868C>G		intron	N/A	NP_071286.1
	FXYD6-FXYD2	NM_001204268.3		c.-6+15868C>G		intron	N/A	NP_001191197.1
	FXYD6-FXYD2	NM_001243598.4		c.-6+15868C>G		intron	N/A	NP_001230527.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6	ENST00000526014.6	TSL:1 MANE Select	c.-6+15868C>G		intron	N/A	ENSP00000433312.1
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.-6+15868C>G		intron	N/A	ENSP00000482442.1
	FXYD6	ENST00000260282.8	TSL:1	c.-178-2438C>G		intron	N/A	ENSP00000260282.4

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72888 AN: 152014 Hom.: 18233 Cov.: 33

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.480 AC: 72964 AN: 152132 Hom.: 18265 Cov.: 33 AF XY: 0.486 AC XY: 36116 AN XY: 74372

African (AFR) AF: 0.576 AC: 23870 AN: 41468

American (AMR) AF: 0.518 AC: 7913 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1687 AN: 3472

East Asian (EAS) AF: 0.730 AC: 3779 AN: 5180

South Asian (SAS) AF: 0.619 AC: 2993 AN: 4832

European-Finnish (FIN) AF: 0.441 AC: 4665 AN: 10586

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26441 AN: 67992

Other (OTH) AF: 0.462 AC: 976 AN: 2112

Alfa AF: 0.283 Hom.: 605

Bravo AF: 0.491

Asia WGS AF: 0.658 AC: 2289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.21
DANN	Benign	0.38
PhyloP100		-1.2
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: rs1815774; hg19: chr11-117731439;