chr14-92323733-A-G

Position:

• chr14-92323733-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.-98A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,425,626 control chromosomes in the GnomAD database, including 133,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (10288 hom., cov: 32)
  • Exomes 𝑓: 0.43 (123198 hom.)
• Consequence: SLC24A4 NM_153646.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02

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=-0.81).
• BP6: Variant 14-92323733-A-G is Benign according to our data. Variant chr14-92323733-A-G is described in ClinVar as [Benign]. Clinvar id is 1265331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4	c.-98A>G		5_prime_UTR_variant	1/17	ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6	c.-98A>G		5_prime_UTR_variant	1/17	1	NM_153646.4	A1
SLC24A4	ENST00000393265.6	c.-63+1098A>G		intron_variant		1
SLC24A4	ENST00000531433.5	c.-23-75A>G		intron_variant		2		P4
SLC24A4	ENST00000676001.1	c.-23-75A>G		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49930 AN: 151788 Hom.: 10285 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.297

GnomAD4 exome AF: 0.432 AC: 550381 AN: 1273722 Hom.: 123198 Cov.: 20 AF XY: 0.430 AC XY: 267914 AN XY: 622464

Gnomad4 AFR exome AF: 0.0629

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.571

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.475

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.329 AC: 49931 AN: 151904 Hom.: 10288 Cov.: 32 AF XY: 0.330 AC XY: 24514 AN XY: 74234

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.303

Alfa AF: 0.377 Hom.: 1558

Bravo AF: 0.305

Asia WGS AF: 0.404 AC: 1405 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	-0.81
CADD	Benign	3.4
DANN	Benign	0.31

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: rs12883151; hg19: chr14-92790077;