rs7142084

Variant names:

• chr14-92356687-A-G
• rs7142084
• NM_153646.4:c.241+30709A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-92356687-A-G
• chr14-92356687-A-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.241+30709A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,308 control chromosomes in the GnomAD database, including 58,577 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 0.87 (58577 hom., cov: 33)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.241+30709A>G		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+30709A>G		intron_variant	Intron 2 of 16	1	NM_153646.4	ENSP00000431840.1
SLC24A4	ENST00000393265.6	c.49+30709A>G		intron_variant	Intron 2 of 16	1		ENSP00000376948.2
SLC24A4	ENST00000676001.1	c.241+30709A>G		intron_variant	Intron 3 of 17			ENSP00000502715.1
SLC24A4	ENST00000531433.5	c.241+30709A>G		intron_variant	Intron 3 of 17	2		ENSP00000433302.1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 133002 AN: 152190 Hom.: 58555 Cov.: 33

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.874 AC: 133071 AN: 152308 Hom.: 58577 Cov.: 33 AF XY: 0.877 AC XY: 65319 AN XY: 74466

African (AFR) AF: 0.748 AC: 31083 AN: 41558

American (AMR) AF: 0.928 AC: 14198 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3253 AN: 3472

East Asian (EAS) AF: 0.975 AC: 5053 AN: 5182

South Asian (SAS) AF: 0.880 AC: 4243 AN: 4822

European-Finnish (FIN) AF: 0.934 AC: 9921 AN: 10624

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62292 AN: 68026

Other (OTH) AF: 0.887 AC: 1877 AN: 2116

Alfa AF: 0.894 Hom.: 6500

Bravo AF: 0.871

Asia WGS AF: 0.922 AC: 3207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.34
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: rs7142084; hg19: chr14-92823031;