15-48131886-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_205850.3(SLC24A5):c.302-2372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,232 control chromosomes in the GnomAD database, including 91 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 0.026 (91 hom., cov: 32)
• Consequence: SLC24A5 NM_205850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

Genes affected

SLC24A5 (HGNC:20611): (solute carrier family 24 member 5) This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0258 (3929/152232) while in subpopulation NFE AF= 0.0376 (2557/67996). AF 95% confidence interval is 0.0364. There are 91 homozygotes in gnomad4. There are 1950 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 91 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A5	NM_205850.3	c.302-2372T>C		intron_variant		ENST00000341459.8
SLC24A5	XM_024449901.2	c.-38-2372T>C		intron_variant
SLC24A5	XM_047432394.1	c.302-2372T>C		intron_variant
SLC24A5	XM_047432395.1	c.-38-2372T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A5	ENST00000341459.8	c.302-2372T>C		intron_variant		1	NM_205850.3	P1
SLC24A5	ENST00000449382.2	c.122-2372T>C		intron_variant		1
SLC24A5	ENST00000463289.1	n.62-2372T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3930 AN: 152114 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.00666

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0258 AC: 3929 AN: 152232 Hom.: 91 Cov.: 32 AF XY: 0.0262 AC XY: 1950 AN XY: 74426

Gnomad4 AFR AF: 0.00664

Gnomad4 AMR AF: 0.0238

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0453

Gnomad4 NFE AF: 0.0376

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0316 Hom.: 16

Bravo AF: 0.0235

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.1
Dann	Benign	0.78

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: rs17426596; hg19: chr15-48424083;