14-92326088-T-C

Position:

• chr14-92326088-T-C

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.241+110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.986 in 690,984 control chromosomes in the GnomAD database, including 336,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (69938 hom., cov: 32)
  • Exomes 𝑓: 0.99 (266360 hom.)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0340

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=-0.82).
• BP6: Variant 14-92326088-T-C is Benign according to our data. Variant chr14-92326088-T-C is described in ClinVar as [Benign]. Clinvar id is 1269884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4	c.241+110T>C		intron_variant		ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6	c.241+110T>C		intron_variant		1	NM_153646.4	A1
SLC24A4	ENST00000393265.6	c.49+110T>C		intron_variant		1
SLC24A4	ENST00000531433.5	c.241+110T>C		intron_variant		2		P4
SLC24A4	ENST00000676001.1	c.241+110T>C		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.956 AC: 145514 AN: 152166 Hom.: 69891 Cov.: 32

Gnomad AFR AF: 0.849

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.966

GnomAD4 exome AF: 0.994 AC: 535519 AN: 538700 Hom.: 266360 AF XY: 0.995 AC XY: 280298 AN XY: 281694

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.989

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.986

GnomAD4 genome AF: 0.956 AC: 145619 AN: 152284 Hom.: 69938 Cov.: 32 AF XY: 0.958 AC XY: 71339 AN XY: 74472

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.982

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.966

Alfa AF: 0.967 Hom.: 9568

Bravo AF: 0.950

Asia WGS AF: 0.989 AC: 3439 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	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.69

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: rs941645; hg19: chr14-92792432;