rs2675348

Variant names:

• chr15-48128547-A-G
• rs2675348
• NM_205850.3:c.302-5711A>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.302-5711A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,128 control chromosomes in the GnomAD database, including 8,137 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 0.20 (8137 hom., cov: 32)
• Consequence: SLC24A5 NM_205850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.302-5711A>G		intron_variant	Intron 2 of 8	ENST00000341459.8	NP_995322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.302-5711A>G		intron_variant	Intron 2 of 8	1	NM_205850.3	ENSP00000341550.3
SLC24A5	ENST00000449382.2	c.122-5711A>G		intron_variant	Intron 1 of 7	1		ENSP00000389966.2
SLC24A5	ENST00000463289.1	n.62-5711A>G		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30336 AN: 152010 Hom.: 8109 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.200 AC: 30426 AN: 152128 Hom.: 8137 Cov.: 32 AF XY: 0.200 AC XY: 14911 AN XY: 74382

African (AFR) AF: 0.580 AC: 24039 AN: 41428

American (AMR) AF: 0.169 AC: 2591 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.477 AC: 2466 AN: 5170

South Asian (SAS) AF: 0.162 AC: 782 AN: 4824

European-Finnish (FIN) AF: 0.00414 AC: 44 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00212 AC: 144 AN: 68014

Other (OTH) AF: 0.168 AC: 355 AN: 2112

Alfa AF: 0.0752 Hom.: 8015

Bravo AF: 0.230

Asia WGS AF: 0.403 AC: 1390 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	14
DANN	Benign	0.61
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2675348; hg19: chr15-48420744;