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GeneBe

14-92433913-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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

2
Splicing: ADA: 0.00004551
2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.71 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 55 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC24A4NM_153646.4 linkuse as main transcriptc.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
SLC24A4ENST00000532405.6 linkuse as main transcriptc.243G>A p.Ala81= splice_region_variant, synonymous_variant 3/171 NM_153646.4 A1Q8NFF2-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0145
AC:
2211
AN:
152130
Hom.:
55
Cov.:
32
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.:
23
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.:
49
Cov.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0146
AC:
2216
AN:
152248
Hom.:
55
Cov.:
32
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.:
10
Bravo
AF:
0.0165
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.000491
EpiControl
AF:
0.000415

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 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.

Other links and lift over

dbSNP: rs77425477; hg19: chr14-92900257; API