Variant 14-92433913-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_153646.4(SLC24A4):c.243G>A(p.Ala81=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,613,928 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 55 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 49 hom. )

Consequence

SLC24A4
NM_153646.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00004551

Clinical Significance

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

Conservation

PhyloP100: -2.71

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 14-92433913-G-A is Benign according to our data. Variant chr14-92433913-G-A is described in ClinVar as [Benign]. Clinvar id is 788581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.71 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0146 (2216/152248) while in subpopulation AFR AF= 0.0503 (2087/41526). AF 95% confidence interval is 0.0485. There are 55 homozygotes in gnomad4. There are 982 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4 linkuse as main transcript	c.243G>A	p.Ala81=	splice_region_variant, synonymous_variant	3/17	ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6 linkuse as main transcript	c.243G>A	p.Ala81=	splice_region_variant, synonymous_variant	3/17	1	NM_153646.4	A1	Q8NFF2-1

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2211

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00394

AC:

992

AN:

251474

Hom.:

AF XY:

0.00293

AC XY:

398

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0522

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000360

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00164

AC:

2402

AN:

1461680

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1031

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0520

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000258

Gnomad4 OTH exome

AF:

0.00303

GnomAD4 genome

AF:

0.0146

AC:

2216

AN:

152248

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

982

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0503

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00282

Hom.:

Bravo

AF:

0.0165

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.083

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000046

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over