20-49878113-A-G

Variant names:

• chr20-49878113-A-G
• rs6020100
• NM_015266.3:c.1158+50A>G

Variant summary

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

The NM_015266.3(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 NM_015266.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 6 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015266.3. 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.1158+50A>G		intron	N/A	NP_056081.1
	SLC9A8	NM_001260491.2		c.1206+50A>G		intron	N/A	NP_001247420.1
	SLC9A8	NR_048537.2		n.1218+50A>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.1158+50A>G		intron	N/A	ENSP00000354966.2
	SLC9A8	ENST00000417961.5	TSL:2	c.1206+50A>G		intron	N/A	ENSP00000416418.1

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

GnomAD2 exomes AF: 0.366 AC: 60571 AN: 165596 AF XY: 0.364

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 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

African (AFR) AF: 0.568 AC: 12056 AN: 21242

American (AMR) AF: 0.309 AC: 8018 AN: 25928

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 7798 AN: 20334

East Asian (EAS) AF: 0.140 AC: 4787 AN: 34118

South Asian (SAS) AF: 0.235 AC: 14634 AN: 62284

European-Finnish (FIN) AF: 0.298 AC: 13026 AN: 43776

Middle Eastern (MID) AF: 0.456 AC: 1696 AN: 3716

European-Non Finnish (NFE) AF: 0.410 AC: 294810 AN: 719258

Other (OTH) AF: 0.397 AC: 17006 AN: 42876

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

African (AFR) AF: 0.563 AC: 23201 AN: 41218

American (AMR) AF: 0.368 AC: 5612 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1329 AN: 3468

East Asian (EAS) AF: 0.161 AC: 834 AN: 5174

South Asian (SAS) AF: 0.230 AC: 1105 AN: 4794

European-Finnish (FIN) AF: 0.304 AC: 3120 AN: 10266

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

European-Non Finnish (NFE) AF: 0.408 AC: 27675 AN: 67786

Other (OTH) AF: 0.424 AC: 893 AN: 2106

Alfa AF: 0.400 Hom.: 1750

Bravo AF: 0.441

Asia WGS AF: 0.222 AC: 772 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.63
PhyloP100		0.26
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: rs6020100; hg19: chr20-48494650; COSMIC: COSV64287708;