rs17783630

Positions:

• chr14-92489041-A-C
• chr14-92489041-A-G

Variant summary

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

The NM_153646.4(SLC24A4):​c.1537+2261A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,908 control chromosomes in the GnomAD database, including 20,733 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 0.52 (20733 hom., cov: 30)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.1537+2261A>C		intron_variant		ENST00000532405.6	NP_705932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A4	ENST00000532405.6	c.1537+2261A>C		intron_variant		1	NM_153646.4	ENSP00000431840.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78927 AN: 151790 Hom.: 20719 Cov.: 30

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.520 AC: 78982 AN: 151908 Hom.: 20733 Cov.: 30 AF XY: 0.517 AC XY: 38343 AN XY: 74224

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.507

Alfa AF: 0.547 Hom.: 33819

Bravo AF: 0.510

Asia WGS AF: 0.398 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.54

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: rs17783630; hg19: chr14-92955385;