rs17783630

Variant names:

• chr14-92489041-A-C
• rs17783630
• NM_153646.4:c.1537+2261A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-92489041-A-C
• chr14-92489041-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153646.4(SLC24A4):​c.1537+2261A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,908 control chromosomes in the GnomAD database, including 20,733 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (20733 hom., cov: 30)
• Consequence: SLC24A4 NM_153646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 27 publications found

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]

SLC24A4 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta hypomaturation type 2A5

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• amelogenesis imperfecta, type 3A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A4	NM_153646.4	c.1537+2261A>C		intron_variant	Intron 14 of 16	ENST00000532405.6	NP_705932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A4	ENST00000532405.6	c.1537+2261A>C		intron_variant	Intron 14 of 16	1	NM_153646.4	ENSP00000431840.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78927 AN: 151790 Hom.: 20719 Cov.: 30

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.520 AC: 78982 AN: 151908 Hom.: 20733 Cov.: 30 AF XY: 0.517 AC XY: 38343 AN XY: 74224

African (AFR) AF: 0.487 AC: 20191 AN: 41420

American (AMR) AF: 0.472 AC: 7198 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1699 AN: 3472

East Asian (EAS) AF: 0.345 AC: 1776 AN: 5154

South Asian (SAS) AF: 0.472 AC: 2272 AN: 4818

European-Finnish (FIN) AF: 0.570 AC: 6008 AN: 10534

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38096 AN: 67936

Other (OTH) AF: 0.507 AC: 1068 AN: 2108

Alfa AF: 0.546 Hom.: 46364

Bravo AF: 0.510

Asia WGS AF: 0.398 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17783630; hg19: chr14-92955385;