11-117829608-A-G

Variant names:

• chr11-117829608-A-G
• rs4472969
• ENST00000614497.5:c.260-6891T>C

Variant summary

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

The NM_001204268.3(FXYD6-FXYD2):​c.260-6891T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 151,306 control chromosomes in the GnomAD database, including 51,699 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 0.82 (51699 hom., cov: 27)
• Consequence: FXYD6-FXYD2 NM_001204268.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXYD6-FXYD2	NM_001204268.3	c.260-6891T>C		intron_variant	Intron 6 of 10		NP_001191197.1
FXYD6-FXYD2	NM_001243598.4	c.273-6891T>C		intron_variant	Intron 6 of 9		NP_001230527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXYD6-FXYD2	ENST00000614497.5	c.260-6891T>C		intron_variant	Intron 6 of 10	3		ENSP00000482442.1
FXYD6-FXYD2	ENST00000532984.1	c.273-6891T>C		intron_variant	Intron 6 of 9	3		ENSP00000463024.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 124613 AN: 151186 Hom.: 51649 Cov.: 27

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.817

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.824 AC: 124724 AN: 151306 Hom.: 51699 Cov.: 27 AF XY: 0.816 AC XY: 60274 AN XY: 73886

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.879

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.840

Alfa AF: 0.831 Hom.: 70320

Bravo AF: 0.831

Asia WGS AF: 0.765 AC: 2664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.34

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: rs4472969; hg19: chr11-117700323; COSMIC: COSV52642643; COSMIC: COSV52642643;