14-92464820-G-T

Variant names:

• chr14-92464820-G-T
• rs8019291
• NM_153646.4:c.1255+8212G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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: 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=-0.94).
• 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 rank	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.1255+8212G>T		intron_variant	Intron 12 of 16	ENST00000532405.6	NP_705932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A4	ENST00000532405.6	c.1255+8212G>T		intron_variant	Intron 12 of 16	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

African (AFR) AF: 0.182 AC: 7565 AN: 41536

American (AMR) AF: 0.190 AC: 2910 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3468

East Asian (EAS) AF: 0.0841 AC: 434 AN: 5162

South Asian (SAS) AF: 0.202 AC: 976 AN: 4826

European-Finnish (FIN) AF: 0.0776 AC: 823 AN: 10606

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9096 AN: 68000

Other (OTH) AF: 0.157 AC: 332 AN: 2114

Alfa AF: 0.141 Hom.: 6771

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
PhyloP100		-1.3
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: rs8019291; hg19: chr14-92931164;