rs4900132

Variant names:

• chr14-92493894-A-G
• rs4900132
• NM_153646.4:c.*266A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.766
• Publications: 8 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 -20 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 VariationId is 1180048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153646.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A4	NM_153646.4	MANE Select	c.*266A>G		3_prime_UTR	Exon 17 of 17	NP_705932.2
	SLC24A4	NM_001378620.1		c.*266A>G		3_prime_UTR	Exon 18 of 18	NP_001365549.1
	SLC24A4	NM_001425254.1		c.*266A>G		3_prime_UTR	Exon 17 of 17	NP_001412183.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A4	ENST00000532405.6	TSL:1 MANE Select	c.*266A>G		3_prime_UTR	Exon 17 of 17	ENSP00000431840.1
	SLC24A4	ENST00000393265.6	TSL:1	c.*266A>G		3_prime_UTR	Exon 17 of 17	ENSP00000376948.2
	SLC24A4	ENST00000525557.5	TSL:1	c.*436A>G		3_prime_UTR	Exon 15 of 15	ENSP00000432464.1

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

African (AFR) AF: 0.262 AC: 2664 AN: 10154

American (AMR) AF: 0.184 AC: 2092 AN: 11382

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 1980 AN: 10192

East Asian (EAS) AF: 0.242 AC: 5297 AN: 21932

South Asian (SAS) AF: 0.240 AC: 7561 AN: 31548

European-Finnish (FIN) AF: 0.152 AC: 3158 AN: 20720

Middle Eastern (MID) AF: 0.175 AC: 253 AN: 1444

European-Non Finnish (NFE) AF: 0.143 AC: 28037 AN: 196436

Other (OTH) AF: 0.180 AC: 3450 AN: 19154

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

African (AFR) AF: 0.260 AC: 10793 AN: 41492

American (AMR) AF: 0.200 AC: 3066 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3466

East Asian (EAS) AF: 0.311 AC: 1611 AN: 5180

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10586

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9639 AN: 68016

Other (OTH) AF: 0.174 AC: 368 AN: 2112

Alfa AF: 0.176 Hom.: 677

Bravo AF: 0.197

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.043
DANN	Benign	0.50
PhyloP100		-0.77
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: rs4900132; hg19: chr14-92960238;