rs6020100

Positions:

• chr20-49878113-A-G
• chr20-49878113-A-T

Variant summary

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

The ENST00000361573.3(SLC9A8):​c.1158+50A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,124,784 control chromosomes in the GnomAD database, including 89,734 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 0.43 (14552 hom., cov: 30)
  • Exomes 𝑓: 0.38 (75182 hom.)
• Consequence: SLC9A8 ENST00000361573.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A8	NM_015266.3	c.1158+50A>G		intron_variant		ENST00000361573.3	NP_056081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A8	ENST00000361573.3	c.1158+50A>G		intron_variant		1	NM_015266.3	ENSP00000354966	P1
SLC9A8	ENST00000417961.5	c.1206+50A>G		intron_variant		2		ENSP00000416418

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64351 AN: 151144 Hom.: 14543 Cov.: 30

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.425

GnomAD3 exomes AF: 0.366 AC: 60571 AN: 165596 Hom.: 11885 AF XY: 0.364 AC XY: 33295 AN XY: 91380

Gnomad AFR exome AF: 0.566

Gnomad AMR exome AF: 0.291

Gnomad ASJ exome AF: 0.385

Gnomad EAS exome AF: 0.140

Gnomad SAS exome AF: 0.240

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.419

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.384 AC: 373831 AN: 973532 Hom.: 75182 Cov.: 12 AF XY: 0.379 AC XY: 189737 AN XY: 499982

Gnomad4 AFR exome AF: 0.568

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.383

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.426 AC: 64395 AN: 151252 Hom.: 14552 Cov.: 30 AF XY: 0.415 AC XY: 30618 AN XY: 73858

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.424

Alfa AF: 0.394 Hom.: 1628

Bravo AF: 0.441

Asia WGS AF: 0.222 AC: 772 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.63

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: rs6020100; hg19: chr20-48494650; COSMIC: COSV64287708;