20-49886924-T-C

Position:

• chr20-49886924-T-C

Variant summary

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

The NM_015266.3(SLC9A8):​c.1638+26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0774 in 1,602,330 control chromosomes in the GnomAD database, including 5,293 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 0.098 (897 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4396 hom.)
• Consequence: SLC9A8 NM_015266.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9A8	NM_015266.3	c.1638+26T>C		intron_variant		ENST00000361573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9A8	ENST00000361573.3	c.1638+26T>C		intron_variant		1	NM_015266.3	P1
SLC9A8	ENST00000417961.5	c.1686+26T>C		intron_variant		2
SLC9A8	ENST00000490250.1	n.528+26T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14854 AN: 152074 Hom.: 890 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0403

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0729

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.0816 AC: 19824 AN: 242978 Hom.: 983 AF XY: 0.0803 AC XY: 10531 AN XY: 131174

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.0738

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.0373

Gnomad SAS exome AF: 0.0816

Gnomad FIN exome AF: 0.0753

Gnomad NFE exome AF: 0.0751

Gnomad OTH exome AF: 0.0841

GnomAD4 exome AF: 0.0753 AC: 109150 AN: 1450138 Hom.: 4396 Cov.: 31 AF XY: 0.0757 AC XY: 54507 AN XY: 719996

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0744

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.0413

Gnomad4 SAS exome AF: 0.0822

Gnomad4 FIN exome AF: 0.0755

Gnomad4 NFE exome AF: 0.0716

Gnomad4 OTH exome AF: 0.0768

GnomAD4 genome AF: 0.0979 AC: 14902 AN: 152192 Hom.: 897 Cov.: 32 AF XY: 0.0959 AC XY: 7137 AN XY: 74412

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0401

Gnomad4 SAS AF: 0.0804

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.0730

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0928 Hom.: 152

Bravo AF: 0.101

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.41

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: rs7270636; hg19: chr20-48503461;