14-92434161-A-T

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.318+173A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,072 control chromosomes in the GnomAD database, including 40,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.73 (40975 hom., cov: 31)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.402

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=-0.92).
• BP6: Variant 14-92434161-A-T is Benign according to our data. Variant chr14-92434161-A-T is described in ClinVar as [Benign]. Clinvar id is 1180238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4	c.318+173A>T		intron_variant		ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6	c.318+173A>T		intron_variant		1	NM_153646.4	A1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111126 AN: 151954 Hom.: 40931 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.733

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.731 AC: 111231 AN: 152072 Hom.: 40975 Cov.: 31 AF XY: 0.738 AC XY: 54852 AN XY: 74304

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.737

Alfa AF: 0.695 Hom.: 4341

Bravo AF: 0.737

Asia WGS AF: 0.881 AC: 3063 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	-0.92
Cadd	Benign	0.97
Dann	Benign	0.72

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: rs7151618; hg19: chr14-92900505;