dbSNP rs941650: SLC24A4:p.His165His (chr14-92442729-T-C) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BA1

The NM_153646.4(SLC24A4):c.495T>C(p.His165His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,612,880 control chromosomes in the GnomAD database, including 465,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 47832 hom., cov: 32)

Exomes 𝑓: 0.75 ( 417515 hom. )

Consequence

SLC24A4
NM_153646.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.62

Publications

20 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.255).

BP6

Variant 14-92442729-T-C is Benign according to our data. Variant chr14-92442729-T-C is described in ClinVar as Benign. ClinVar VariationId is 1278578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A4	NM_153646.4 link	c.495T>C	p.His165His	synonymous_variant	Exon 6 of 17	ENST00000532405.6	NP_705932.2	Q8NFF2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A4	ENST00000532405.6 link	c.495T>C	p.His165His	synonymous_variant	Exon 6 of 17	1	NM_153646.4	ENSP00000431840.1		Q8NFF2-1

Frequencies

GnomAD3 genomes

AF:

0.790

AC:

120097

AN:

152048

Hom.:

47778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.861

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.802

Gnomad ASJ

AF:

0.783

Gnomad EAS

AF:

0.983

Gnomad SAS

AF:

0.862

Gnomad FIN

AF:

0.756

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.729

Gnomad OTH

AF:

0.796

GnomAD2 exomes

AF:

0.791

AC:

198659

AN:

251230

AF XY:

0.792

show subpopulations

Gnomad AFR exome

AF:

0.861

Gnomad AMR exome

AF:

0.814

Gnomad ASJ exome

AF:

0.787

Gnomad EAS exome

AF:

0.983

Gnomad FIN exome

AF:

0.750

Gnomad NFE exome

AF:

0.736

Gnomad OTH exome

AF:

0.784

GnomAD4 exome

AF:

0.754

AC:

1101170

AN:

1460714

Hom.:

417515

Cov.:

AF XY:

0.757

AC XY:

549809

AN XY:

726750

show subpopulations

African (AFR)

AF:

0.868

AC:

29046

AN:

33456

American (AMR)

AF:

0.814

AC:

36370

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

20546

AN:

26116

East Asian (EAS)

AF:

0.979

AC:

38873

AN:

39692

South Asian (SAS)

AF:

0.844

AC:

72779

AN:

86246

European-Finnish (FIN)

AF:

0.746

AC:

39836

AN:

53408

Middle Eastern (MID)

AF:

0.860

AC:

4957

AN:

5762

European-Non Finnish (NFE)

AF:

0.731

AC:

811875

AN:

1110984

Other (OTH)

AF:

0.777

AC:

46888

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

12576

25152

37728

50304

62880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20128

40256

60384

80512

100640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.790

AC:

120214

AN:

152166

Hom.:

47832

Cov.:

AF XY:

0.794

AC XY:

59040

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.861

AC:

35752

AN:

41506

American (AMR)

AF:

0.803

AC:

12272

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.783

AC:

2719

AN:

3472

East Asian (EAS)

AF:

0.983

AC:

5095

AN:

5182

South Asian (SAS)

AF:

0.863

AC:

4164

AN:

4824

European-Finnish (FIN)

AF:

0.756

AC:

8003

AN:

10582

Middle Eastern (MID)

AF:

0.857

AC:

252

AN:

294

European-Non Finnish (NFE)

AF:

0.729

AC:

49596

AN:

67998

Other (OTH)

AF:

0.799

AC:

1686

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1312

2624

3936

5248

6560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.762

Hom.:

44598

Bravo

AF:

0.799

Asia WGS

AF:

0.908

AC:

3159

AN:

3478

EpiCase

AF:

0.746

EpiControl

AF:

0.752

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.17

(source)

DANN

Benign

0.32

PhyloP100

-2.6

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over