14-92395777-C-T

Variant names:

• chr14-92395777-C-T
• rs1108161
• NM_153646.4:c.242-38135C>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.242-38135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,042 control chromosomes in the GnomAD database, including 790 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 0.097 (790 hom., cov: 32)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.242-38135C>T		intron_variant	Intron 2 of 16	ENST00000532405.6	NP_705932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A4	ENST00000532405.6	c.242-38135C>T		intron_variant	Intron 2 of 16	1	NM_153646.4	ENSP00000431840.1
SLC24A4	ENST00000393265.6	c.50-38135C>T		intron_variant	Intron 2 of 16	1		ENSP00000376948.2
SLC24A4	ENST00000676001.1	c.242-38135C>T		intron_variant	Intron 3 of 17			ENSP00000502715.1
SLC24A4	ENST00000531433.5	c.242-38135C>T		intron_variant	Intron 3 of 17	2		ENSP00000433302.1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14763 AN: 151924 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0909

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0971 AC: 14765 AN: 152042 Hom.: 790 Cov.: 32 AF XY: 0.0960 AC XY: 7132 AN XY: 74318

African (AFR) AF: 0.0742 AC: 3075 AN: 41444

American (AMR) AF: 0.0907 AC: 1387 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3470

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5178

South Asian (SAS) AF: 0.0895 AC: 430 AN: 4806

European-Finnish (FIN) AF: 0.101 AC: 1066 AN: 10564

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7957 AN: 67980

Other (OTH) AF: 0.106 AC: 224 AN: 2110

Alfa AF: 0.104 Hom.: 1001

Bravo AF: 0.0962

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.57
PhyloP100		1.0
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: rs1108161; hg19: chr14-92862121;