14-92439473-A-G

Position:

• chr14-92439473-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153646.4(SLC24A4):​c.393+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 1,474,398 control chromosomes in the GnomAD database, including 415,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46891 hom., cov: 36)
  • Exomes 𝑓: 0.74 (368946 hom.)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.563

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-92439473-A-G is Benign according to our data. Variant chr14-92439473-A-G is described in ClinVar as [Benign]. Clinvar id is 1297840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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/exons	MANE	UniProt
SLC24A4	NM_153646.4	c.393+64A>G		intron_variant		ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6	c.393+64A>G		intron_variant		1	NM_153646.4	A1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118855 AN: 152170 Hom.: 46833 Cov.: 36

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.786

GnomAD4 exome AF: 0.744 AC: 984130 AN: 1322110 Hom.: 368946 AF XY: 0.747 AC XY: 496387 AN XY: 664514

Gnomad4 AFR exome AF: 0.867

Gnomad4 AMR exome AF: 0.811

Gnomad4 ASJ exome AF: 0.781

Gnomad4 EAS exome AF: 0.980

Gnomad4 SAS exome AF: 0.838

Gnomad4 FIN exome AF: 0.740

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.768

GnomAD4 genome AF: 0.781 AC: 118976 AN: 152288 Hom.: 46891 Cov.: 36 AF XY: 0.786 AC XY: 58502 AN XY: 74470

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.789

Alfa AF: 0.734 Hom.: 4885

Bravo AF: 0.791

Asia WGS AF: 0.901 AC: 3133 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.0
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs4900122; hg19: chr14-92905817;