rs4809760

chr20-49838134-A-G

Variant summary

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

The NM_015266.3(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 NM_015266.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A8	NM_015266.3	c.290-1407A>G		intron_variant		ENST00000361573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A8	ENST00000361573.3	c.290-1407A>G		intron_variant		1	NM_015266.3	P1
SLC9A8	ENST00000417961.5	c.290-1407A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.443

Alfa AF: 0.410 Hom.: 7073

Bravo AF: 0.472

Asia WGS AF: 0.371 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.0
Dann	Benign	0.36

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: rs4809760; hg19: chr20-48454671;