chr20-49867704-G-A

Variant names:

• chr20-49867704-G-A
• rs2281223
• NM_015266.3:c.958+2860G>A

Variant summary

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

The NM_015266.3(SLC9A8):​c.958+2860G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,944 control chromosomes in the GnomAD database, including 14,333 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 0.42 (14333 hom., cov: 32)
• Consequence: SLC9A8 NM_015266.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 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.958+2860G>A		intron	N/A	NP_056081.1
	SLC9A8	NM_001260491.2		c.1006+2860G>A		intron	N/A	NP_001247420.1
	SLC9A8	NR_048537.2		n.1018+2860G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A8	ENST00000361573.3	TSL:1 MANE Select	c.958+2860G>A		intron	N/A	ENSP00000354966.2
	SLC9A8	ENST00000417961.5	TSL:2	c.1006+2860G>A		intron	N/A	ENSP00000416418.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64217 AN: 151828 Hom.: 14323 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.423 AC: 64265 AN: 151944 Hom.: 14333 Cov.: 32 AF XY: 0.412 AC XY: 30615 AN XY: 74268

African (AFR) AF: 0.553 AC: 22895 AN: 41438

American (AMR) AF: 0.366 AC: 5587 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3466

East Asian (EAS) AF: 0.162 AC: 834 AN: 5164

South Asian (SAS) AF: 0.233 AC: 1121 AN: 4818

European-Finnish (FIN) AF: 0.310 AC: 3265 AN: 10542

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27729 AN: 67940

Other (OTH) AF: 0.418 AC: 880 AN: 2104

Alfa AF: 0.403 Hom.: 6601

Bravo AF: 0.436

Asia WGS AF: 0.226 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.25
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: rs2281223; hg19: chr20-48484241;