chr20-49867704-G-A

Position:

• chr20-49867704-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A8	NM_015266.3	c.958+2860G>A		intron_variant		ENST00000361573.3	NP_056081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A8	ENST00000361573.3	c.958+2860G>A		intron_variant		1	NM_015266.3	ENSP00000354966	P1
SLC9A8	ENST00000417961.5	c.1006+2860G>A		intron_variant		2		ENSP00000416418

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

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.418

Alfa AF: 0.400 Hom.: 5799

Bravo AF: 0.436

Asia WGS AF: 0.226 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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