rs4406992

chr14-92470276-C-T

Variant summary

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

The NM_153646.4(SLC24A4):c.1256-12404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,038 control chromosomes in the GnomAD database, including 35,682 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 0.67 (35682 hom., cov: 31)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755

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 (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4	c.1256-12404C>T		intron_variant		ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6	c.1256-12404C>T		intron_variant		1	NM_153646.4	A1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102453 AN: 151918 Hom.: 35660 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.674 AC: 102521 AN: 152038 Hom.: 35682 Cov.: 31 AF XY: 0.677 AC XY: 50289 AN XY: 74320

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.685

Alfa AF: 0.739 Hom.: 19096

Bravo AF: 0.660

Asia WGS AF: 0.652 AC: 2268 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	1.1
Dann	Benign	0.34

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: rs4406992; hg19: chr14-92936620;