chr14-92340986-T-C

Variant names:

• chr14-92340986-T-C
• rs11160059
• NM_153646.4:c.241+15008T>C

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+15008T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 152,286 control chromosomes in the GnomAD database, including 73,132 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 0.98 (73132 hom., cov: 31)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 13 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.241+15008T>C		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.241+15008T>C		intron_variant	Intron 2 of 16	1	NM_153646.4	ENSP00000431840.1
SLC24A4	ENST00000393265.6	c.49+15008T>C		intron_variant	Intron 2 of 16	1		ENSP00000376948.2
SLC24A4	ENST00000676001.1	c.241+15008T>C		intron_variant	Intron 3 of 17			ENSP00000502715.1
SLC24A4	ENST00000531433.5	c.241+15008T>C		intron_variant	Intron 3 of 17	2		ENSP00000433302.1

Frequencies

GnomAD3 genomes AF: 0.980 AC: 149071 AN: 152168 Hom.: 73079 Cov.: 31

Gnomad AFR AF: 0.929

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.987

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

GnomAD4 genome AF: 0.980 AC: 149183 AN: 152286 Hom.: 73132 Cov.: 31 AF XY: 0.980 AC XY: 72997 AN XY: 74460

African (AFR) AF: 0.929 AC: 38590 AN: 41526

American (AMR) AF: 0.993 AC: 15193 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3465 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5168 AN: 5168

South Asian (SAS) AF: 1.00 AC: 4830 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68021 AN: 68040

Other (OTH) AF: 0.987 AC: 2086 AN: 2114

Alfa AF: 0.993 Hom.: 14754

Bravo AF: 0.976

Asia WGS AF: 0.996 AC: 3464 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	1.7
DANN	Benign	0.34
PhyloP100		-0.18
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: rs11160059; hg19: chr14-92807330;