rs2555364

Variant names:

• chr15-48127189-C-G
• rs2555364
• NM_205850.3:c.301+5153C>G

Variant summary

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

The NM_205850.3(SLC24A5):​c.301+5153C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,138 control chromosomes in the GnomAD database, including 54,371 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 0.81 (54371 hom., cov: 32)
• Consequence: SLC24A5 NM_205850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.301+5153C>G		intron_variant	Intron 2 of 8	ENST00000341459.8	NP_995322.1
SLC24A5	XM_047432394.1	c.301+5153C>G		intron_variant	Intron 2 of 7		XP_047288350.1
SLC24A5	XM_024449901.2	c.-263C>G		upstream_gene_variant			XP_024305669.2
SLC24A5	XM_047432395.1	c.-347C>G		upstream_gene_variant			XP_047288351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.301+5153C>G		intron_variant	Intron 2 of 8	1	NM_205850.3	ENSP00000341550.3
SLC24A5	ENST00000449382.2	c.121+6024C>G		intron_variant	Intron 1 of 7	1		ENSP00000389966.2
SLC24A5	ENST00000463289.1	n.61+5153C>G		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122968 AN: 152020 Hom.: 54373 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.808 AC: 122997 AN: 152138 Hom.: 54371 Cov.: 32 AF XY: 0.808 AC XY: 60068 AN XY: 74382

African (AFR) AF: 0.449 AC: 18588 AN: 41420

American (AMR) AF: 0.834 AC: 12749 AN: 15288

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3471 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2689 AN: 5152

South Asian (SAS) AF: 0.837 AC: 4039 AN: 4828

European-Finnish (FIN) AF: 0.996 AC: 10582 AN: 10626

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67902 AN: 68036

Other (OTH) AF: 0.841 AC: 1777 AN: 2112

Alfa AF: 0.896 Hom.: 7955

Bravo AF: 0.779

Asia WGS AF: 0.601 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.57
PhyloP100		-0.28
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: rs2555364; hg19: chr15-48419386;