14-92326295-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153646.4(SLC24A4):c.241+317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 152,286 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.035 (108 hom., cov: 32)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.14

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=-0.83).
• BP6: Variant 14-92326295-T-C is Benign according to our data. Variant chr14-92326295-T-C is described in ClinVar as [Benign]. Clinvar id is 1251647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0346 (5271/152286) while in subpopulation NFE AF= 0.0502 (3418/68024). AF 95% confidence interval is 0.0488. There are 108 homozygotes in gnomad4. There are 2522 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 108 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4	c.241+317T>C		intron_variant		ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6	c.241+317T>C		intron_variant		1	NM_153646.4	A1
SLC24A4	ENST00000393265.6	c.49+317T>C		intron_variant		1
SLC24A4	ENST00000531433.5	c.241+317T>C		intron_variant		2		P4
SLC24A4	ENST00000676001.1	c.241+317T>C		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5272 AN: 152168 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.00924

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.0215

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0346 AC: 5271 AN: 152286 Hom.: 108 Cov.: 32 AF XY: 0.0339 AC XY: 2522 AN XY: 74456

Gnomad4 AFR AF: 0.00922

Gnomad4 AMR AF: 0.0433

Gnomad4 ASJ AF: 0.0204

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.0351

Gnomad4 NFE AF: 0.0502

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0435 Hom.: 19

Bravo AF: 0.0339

Asia WGS AF: 0.0240 AC: 83 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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.1
Dann	Benign	0.42

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: rs118164045; hg19: chr14-92792639;