rs7142084

Positions:

• chr14-92356687-A-G
• chr14-92356687-A-T

Variant summary

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

The ENST00000532405.6(SLC24A4):​c.241+30709A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,308 control chromosomes in the GnomAD database, including 58,577 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 0.87 (58577 hom., cov: 33)
• Consequence: SLC24A4 ENST00000532405.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.241+30709A>G		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+30709A>G		intron_variant		1	NM_153646.4	ENSP00000431840	A1
SLC24A4	ENST00000393265.6	c.49+30709A>G		intron_variant		1		ENSP00000376948
SLC24A4	ENST00000531433.5	c.241+30709A>G		intron_variant		2		ENSP00000433302	P4
SLC24A4	ENST00000676001.1	c.241+30709A>G		intron_variant				ENSP00000502715	A1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 133002 AN: 152190 Hom.: 58555 Cov.: 33

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.874 AC: 133071 AN: 152308 Hom.: 58577 Cov.: 33 AF XY: 0.877 AC XY: 65319 AN XY: 74466

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.880

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.916

Gnomad4 OTH AF: 0.887

Alfa AF: 0.901 Hom.: 6282

Bravo AF: 0.871

Asia WGS AF: 0.922 AC: 3207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
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: rs7142084; hg19: chr14-92823031;