rs4809760

Variant names:

• chr20-49838134-A-G
• rs4809760
• NM_015266.3:c.290-1407A>G

Variant summary

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

The ENST00000361573.3(SLC9A8):​c.290-1407A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,004 control chromosomes in the GnomAD database, including 16,224 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 0.45 (16224 hom., cov: 32)
• Consequence: SLC9A8 ENST00000361573.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• Publications: 9 publications found

Genes affected

SLC9A8 (HGNC:20728): (solute carrier family 9 member A8) Sodium-hydrogen exchangers (NHEs), such as SLC9A8, are integral transmembrane proteins that exchange extracellular Na+ for intracellular H+. NHEs have multiple functions, including intracellular pH homeostasis, cell volume regulation, and electroneutral NaCl absorption in epithelia (Xu et al., 2008 [PubMed 18209477]).[supplied by OMIM, Apr 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361573.3. 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
	SLC9A8	NM_015266.3	MANE Select	c.290-1407A>G		intron	N/A	NP_056081.1
	SLC9A8	NM_001260491.2		c.290-1407A>G		intron	N/A	NP_001247420.1
	SLC9A8	NR_048537.2		n.385-1407A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A8	ENST00000361573.3	TSL:1 MANE Select	c.290-1407A>G		intron	N/A	ENSP00000354966.2
	SLC9A8	ENST00000417961.5	TSL:2	c.290-1407A>G		intron	N/A	ENSP00000416418.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68809 AN: 151886 Hom.: 16215 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.453 AC: 68854 AN: 152004 Hom.: 16224 Cov.: 32 AF XY: 0.445 AC XY: 33104 AN XY: 74322

African (AFR) AF: 0.581 AC: 24046 AN: 41422

American (AMR) AF: 0.430 AC: 6558 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2655 AN: 5178

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3483 AN: 10564

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27909 AN: 67972

Other (OTH) AF: 0.443 AC: 935 AN: 2110

Alfa AF: 0.412 Hom.: 7909

Bravo AF: 0.472

Asia WGS AF: 0.371 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.36
PhyloP100		0.20
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: rs4809760; hg19: chr20-48454671;