NM_153646.4:c.1255+11470C>G

Variant names:

• chr14-92468078-C-G
• rs7154288
• NM_153646.4:c.1255+11470C>G

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+11470C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,070 control chromosomes in the GnomAD database, including 46,926 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 0.78 (46926 hom., cov: 32)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.1255+11470C>G		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+11470C>G		intron_variant	Intron 12 of 16	1	NM_153646.4	ENSP00000431840.1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118223 AN: 151952 Hom.: 46905 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.778 AC: 118291 AN: 152070 Hom.: 46926 Cov.: 32 AF XY: 0.779 AC XY: 57917 AN XY: 74346

African (AFR) AF: 0.613 AC: 25357 AN: 41392

American (AMR) AF: 0.786 AC: 12008 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2758 AN: 3472

East Asian (EAS) AF: 0.746 AC: 3860 AN: 5172

South Asian (SAS) AF: 0.769 AC: 3708 AN: 4822

European-Finnish (FIN) AF: 0.878 AC: 9319 AN: 10610

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58655 AN: 68010

Other (OTH) AF: 0.792 AC: 1672 AN: 2110

Alfa AF: 0.819 Hom.: 6409

Bravo AF: 0.762

Asia WGS AF: 0.748 AC: 2602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.88
PhyloP100		-0.028
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: rs7154288; hg19: chr14-92934422;