20-49885069-A-G

Variant names:

• chr20-49885069-A-G
• rs645544
• NM_015266.3:c.1491+1003A>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.1491+1003A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,132 control chromosomes in the GnomAD database, including 19,056 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 0.49 (19056 hom., cov: 33)
• Consequence: SLC9A8 NM_015266.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A8	NM_015266.3	MANE Select	c.1491+1003A>G		intron	N/A	NP_056081.1	Q9Y2E8-1
	SLC9A8	NM_001260491.2		c.1539+1003A>G		intron	N/A	NP_001247420.1	Q9Y2E8-2
	SLC9A8	NR_048537.2		n.1551+1003A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A8	ENST00000361573.3	TSL:1 MANE Select	c.1491+1003A>G		intron	N/A	ENSP00000354966.2	Q9Y2E8-1
	SLC9A8	ENST00000851371.1		c.1590+1003A>G		intron	N/A	ENSP00000521430.1
	SLC9A8	ENST00000417961.5	TSL:2	c.1539+1003A>G		intron	N/A	ENSP00000416418.1	Q9Y2E8-2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74206 AN: 152014 Hom.: 19043 Cov.: 33

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.488 AC: 74262 AN: 152132 Hom.: 19056 Cov.: 33 AF XY: 0.502 AC XY: 37322 AN XY: 74350

African (AFR) AF: 0.371 AC: 15409 AN: 41494

American (AMR) AF: 0.564 AC: 8627 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1726 AN: 3470

East Asian (EAS) AF: 0.775 AC: 4005 AN: 5170

South Asian (SAS) AF: 0.705 AC: 3400 AN: 4824

European-Finnish (FIN) AF: 0.638 AC: 6764 AN: 10596

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32825 AN: 67976

Other (OTH) AF: 0.494 AC: 1044 AN: 2112

Alfa AF: 0.468 Hom.: 24076

Bravo AF: 0.473

Asia WGS AF: 0.724 AC: 2516 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.26
PhyloP100		-1.4
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: rs645544; hg19: chr20-48501606;