NM_001011552.4:c.721-6144A>G

Variant names:

• chr2-102497304-A-G
• rs7583683
• NM_001011552.4:c.721-6144A>G

Variant summary

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

The NM_001011552.4(SLC9A4):​c.721-6144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,068 control chromosomes in the GnomAD database, including 1,841 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 0.15 (1841 hom., cov: 33)
• Consequence: SLC9A4 NM_001011552.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 5 publications found

Genes affected

SLC9A4 (HGNC:11077): (solute carrier family 9 member A4) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to act upstream of or within epithelial cell development and gastric acid secretion. Predicted to be located in several cellular components, including apical plasma membrane; basolateral plasma membrane; and vacuolar membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011552.4. 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
	SLC9A4	NM_001011552.4	MANE Select	c.721-6144A>G		intron	N/A	NP_001011552.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A4	ENST00000295269.5	TSL:1 MANE Select	c.721-6144A>G		intron	N/A	ENSP00000295269.4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22057 AN: 151950 Hom.: 1838 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0901

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.145 AC: 22071 AN: 152068 Hom.: 1841 Cov.: 33 AF XY: 0.141 AC XY: 10449 AN XY: 74356

African (AFR) AF: 0.222 AC: 9208 AN: 41464

American (AMR) AF: 0.108 AC: 1645 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3468

East Asian (EAS) AF: 0.0235 AC: 122 AN: 5192

South Asian (SAS) AF: 0.113 AC: 544 AN: 4830

European-Finnish (FIN) AF: 0.0901 AC: 955 AN: 10604

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8746 AN: 67922

Other (OTH) AF: 0.131 AC: 276 AN: 2110

Alfa AF: 0.134 Hom.: 242

Bravo AF: 0.150

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.74
PhyloP100		0.20
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: rs7583683; hg19: chr2-103113763;