rs12586368

Positions:

• chr14-92348113-G-A

Variant summary

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

The NM_153646.4(SLC24A4):​c.241+22135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,086 control chromosomes in the GnomAD database, including 1,547 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 0.13 (1547 hom., cov: 32)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4	c.241+22135G>A		intron_variant		ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6	c.241+22135G>A		intron_variant		1	NM_153646.4	A1
SLC24A4	ENST00000393265.6	c.49+22135G>A		intron_variant		1
SLC24A4	ENST00000531433.5	c.241+22135G>A		intron_variant		2		P4
SLC24A4	ENST00000676001.1	c.241+22135G>A		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20138 AN: 151966 Hom.: 1544 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.133 AC: 20157 AN: 152086 Hom.: 1547 Cov.: 32 AF XY: 0.134 AC XY: 9978 AN XY: 74346

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.0991

Gnomad4 OTH AF: 0.131

Alfa AF: 0.108 Hom.: 622

Bravo AF: 0.130

Asia WGS AF: 0.134 AC: 466 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	0.33
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: rs12586368; hg19: chr14-92814457;