rs2402130

Positions:

• chr14-92334859-G-A
• chr14-92334859-G-C
• chr14-92334859-G-T

Variant summary

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

The NM_153646.4(SLC24A4):​c.241+8881G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 151,896 control chromosomes in the GnomAD database, including 41,311 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 0.72 (41311 hom., cov: 31)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

Genes affected

SLC24A4 (HGNC:10978): (solute carrier family 24 member 4) This gene encodes a sodium/potassium/calcium exchange protein. The encoded antiporter transports one calcium and one potassium ion in exchange for four sodium ions and has been implicated in amelogenesis and enamel maturation. Certain variants in this gene have been associated with skin, hair, and eye pigmentation, while other variants have been identified in people with hypomaturation-type amelogenesis imperfecta. [provided by RefSeq, Nov 2023]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.241+8881G>A		intron_variant		ENST00000532405.6	NP_705932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A4	ENST00000532405.6	c.241+8881G>A		intron_variant		1	NM_153646.4	ENSP00000431840	A1
SLC24A4	ENST00000393265.6	c.49+8881G>A		intron_variant		1		ENSP00000376948
SLC24A4	ENST00000531433.5	c.241+8881G>A		intron_variant		2		ENSP00000433302	P4
SLC24A4	ENST00000676001.1	c.241+8881G>A		intron_variant				ENSP00000502715	A1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109078 AN: 151778 Hom.: 41300 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.718 AC: 109109 AN: 151896 Hom.: 41311 Cov.: 31 AF XY: 0.726 AC XY: 53931 AN XY: 74238

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.819

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.861

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.741

Alfa AF: 0.785 Hom.: 65492

Bravo AF: 0.702

Asia WGS AF: 0.849 AC: 2952 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.75

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: rs2402130; hg19: chr14-92801203;