15-48131886-T-C

Variant names:

• chr15-48131886-T-C
• rs17426596
• NM_205850.3:c.302-2372T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

SLC24A5 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 91 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205850.3. 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
	SLC24A5	NM_205850.3	MANE Select	c.302-2372T>C		intron	N/A	NP_995322.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A5	ENST00000341459.8	TSL:1 MANE Select	c.302-2372T>C		intron	N/A	ENSP00000341550.3
	SLC24A5	ENST00000449382.2	TSL:1	c.122-2372T>C		intron	N/A	ENSP00000389966.2
	SLC24A5	ENST00000463289.1	TSL:3	n.62-2372T>C		intron	N/A

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

African (AFR) AF: 0.00664 AC: 276 AN: 41550

American (AMR) AF: 0.0238 AC: 363 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4828

European-Finnish (FIN) AF: 0.0453 AC: 481 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0376 AC: 2557 AN: 67996

Other (OTH) AF: 0.0246 AC: 52 AN: 2110

Alfa AF: 0.0335 Hom.: 115

Bravo AF: 0.0235

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.78
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism

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: rs17426596; hg19: chr15-48424083;