rs4900132

chr14-92493894-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153646.4(SLC24A4):c.*266A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 475,144 control chromosomes in the GnomAD database, including 8,093 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3095 hom., cov: 34)
  • Exomes 𝑓: 0.17 (4998 hom.)
• Consequence: SLC24A4 NM_153646.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.766

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-92493894-A-G is Benign according to our data. Variant chr14-92493894-A-G is described in ClinVar as [Benign]. Clinvar id is 1180048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4	c.*266A>G		3_prime_UTR_variant	17/17	ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6	c.*266A>G		3_prime_UTR_variant	17/17	1	NM_153646.4	A1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29265 AN: 152064 Hom.: 3091 Cov.: 34

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.169 AC: 54492 AN: 322962 Hom.: 4998 Cov.: 0 AF XY: 0.172 AC XY: 29080 AN XY: 168620

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.192 AC: 29287 AN: 152182 Hom.: 3095 Cov.: 34 AF XY: 0.197 AC XY: 14631 AN XY: 74392

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.174

Alfa AF: 0.171 Hom.: 540

Bravo AF: 0.197

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.84
Cadd	Benign	0.043
Dann	Benign	0.50

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: rs4900132; hg19: chr14-92960238;