chr14-92334859-G-A

Variant names:

• chr14-92334859-G-A
• rs2402130
• NM_153646.4:c.241+8881G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153646.4(SLC24A4):​c.241+8881G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 151,896 control chromosomes in the GnomAD database, including 41,311 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 0.72 (41311 hom., cov: 31)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 35 publications found

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 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta hypomaturation type 2A5

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• amelogenesis imperfecta, type 3A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153646.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A4	NM_153646.4	MANE Select	c.241+8881G>A		intron	N/A	NP_705932.2	Q8NFF2-1
	SLC24A4	NM_001378620.1		c.241+8881G>A		intron	N/A	NP_001365549.1	Q8NFF2-1
	SLC24A4	NM_001425254.1		c.241+8881G>A		intron	N/A	NP_001412183.1	Q8NFF2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A4	ENST00000532405.6	TSL:1 MANE Select	c.241+8881G>A		intron	N/A	ENSP00000431840.1	Q8NFF2-1
	SLC24A4	ENST00000393265.6	TSL:1	c.49+8881G>A		intron	N/A	ENSP00000376948.2	Q8NFF2-2
	SLC24A4	ENST00000676001.1		c.241+8881G>A		intron	N/A	ENSP00000502715.1	Q8NFF2-1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109078 AN: 151778 Hom.: 41300 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.718 AC: 109109 AN: 151896 Hom.: 41311 Cov.: 31 AF XY: 0.726 AC XY: 53931 AN XY: 74238

African (AFR) AF: 0.460 AC: 19007 AN: 41342

American (AMR) AF: 0.789 AC: 12042 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2837 AN: 3464

East Asian (EAS) AF: 0.933 AC: 4824 AN: 5168

South Asian (SAS) AF: 0.849 AC: 4085 AN: 4814

European-Finnish (FIN) AF: 0.861 AC: 9100 AN: 10566

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54594 AN: 67962

Other (OTH) AF: 0.741 AC: 1564 AN: 2110

Alfa AF: 0.757 Hom.: 89187

Bravo AF: 0.702

Asia WGS AF: 0.849 AC: 2952 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.75
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2402130; hg19: chr14-92801203;