dbSNP rs12586368: SLC24A4:c.241+22135G>A (chr14-92348113-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_153646.4(SLC24A4):c.241+22135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,086 control chromosomes in the GnomAD database, including 1,547 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 0.13 ( 1547 hom., cov: 32)

Consequence

SLC24A4
NM_153646.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

3 publications found

Variant links:

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

SLC24A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) 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 link	c.241+22135G>A		intron_variant	Intron 2 of 16	ENST00000532405.6	NP_705932.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLC24A4	ENST00000532405.6 link	c.241+22135G>A	intron_variant	Intron 2 of 16	1	NM_153646.4	ENSP00000431840.1
SLC24A4	ENST00000393265.6 link	c.49+22135G>A	intron_variant	Intron 2 of 16	1		ENSP00000376948.2
SLC24A4	ENST00000676001.1 link	c.241+22135G>A	intron_variant	Intron 3 of 17			ENSP00000502715.1
SLC24A4	ENST00000531433.5 link	c.241+22135G>A	intron_variant	Intron 3 of 17	2		ENSP00000433302.1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20138

AN:

151966

Hom.:

1544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0779

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0991

Gnomad OTH

AF:

0.133

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

GnomAD4 genome

AF:

0.133

AC:

20157

AN:

152086

Hom.:

1547

Cov.:

AF XY:

0.134

AC XY:

9978

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.196

AC:

8114

AN:

41448

American (AMR)

AF:

0.0777

AC:

1189

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

380

AN:

3468

East Asian (EAS)

AF:

0.147

AC:

762

AN:

5176

South Asian (SAS)

AF:

0.127

AC:

613

AN:

4826

European-Finnish (FIN)

AF:

0.186

AC:

1961

AN:

10568

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0991

AC:

6740

AN:

67990

Other (OTH)

AF:

0.131

AC:

275

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

871

1742

2614

3485

4356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.108

Hom.:

1040

Bravo

AF:

0.130

Asia WGS

AF:

0.134

AC:

466

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.33

(source)

DANN

Benign

0.63

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over