11-117829163-C-T

Variant names:

• chr11-117829163-C-T
• rs2019655
• ENST00000614497.5:c.260-6446G>A

Variant summary

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

The ENST00000614497.5(FXYD6-FXYD2):​c.260-6446G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,208 control chromosomes in the GnomAD database, including 3,310 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 0.19 (3310 hom., cov: 33)
• Consequence: FXYD6-FXYD2 ENST00000614497.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 5 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXYD6-FXYD2	NM_001204268.3	c.260-6446G>A		intron_variant	Intron 6 of 10		NP_001191197.1
FXYD6-FXYD2	NM_001243598.4	c.273-6446G>A		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.260-6446G>A		intron_variant	Intron 6 of 10	3		ENSP00000482442.1
FXYD6-FXYD2	ENST00000532984.1	c.273-6446G>A		intron_variant	Intron 6 of 9	3		ENSP00000463024.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28970 AN: 152090 Hom.: 3303 Cov.: 33

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.190 AC: 28989 AN: 152208 Hom.: 3310 Cov.: 33 AF XY: 0.191 AC XY: 14225 AN XY: 74400

African (AFR) AF: 0.0719 AC: 2989 AN: 41556

American (AMR) AF: 0.182 AC: 2782 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1226 AN: 3464

East Asian (EAS) AF: 0.250 AC: 1291 AN: 5162

South Asian (SAS) AF: 0.300 AC: 1440 AN: 4808

European-Finnish (FIN) AF: 0.210 AC: 2231 AN: 10610

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16213 AN: 67988

Other (OTH) AF: 0.226 AC: 478 AN: 2116

Alfa AF: 0.224 Hom.: 6979

Bravo AF: 0.183

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.56
PhyloP100		-1.1
PromoterAI		-0.011	Neutral
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: rs2019655; hg19: chr11-117699878;