14-92464820-G-T

Position:

• chr14-92464820-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.1255+8212G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,216 control chromosomes in the GnomAD database, including 1,867 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 (1867 hom., cov: 33)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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]

SLC24A4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.1255+8212G>T		intron_variant		ENST00000532405.6	NP_705932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A4	ENST00000532405.6	c.1255+8212G>T		intron_variant		1	NM_153646.4	ENSP00000431840.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23005 AN: 152098 Hom.: 1866 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0841

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0776

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.151 AC: 23019 AN: 152216 Hom.: 1867 Cov.: 33 AF XY: 0.151 AC XY: 11252 AN XY: 74428

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0841

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.0776

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.157

Alfa AF: 0.139 Hom.: 3215

Bravo AF: 0.161

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.65

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: rs8019291; hg19: chr14-92931164;