NM_205850.3:c.301+2127G>A

Variant names:

• chr15-48124163-G-A
• rs2433356
• NM_205850.3:c.301+2127G>A

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+2127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,728 control chromosomes in the GnomAD database, including 3,143 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 0.12 (3143 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC24A5 NM_205850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.301+2127G>A		intron_variant	Intron 2 of 8	ENST00000341459.8	NP_995322.1
SLC24A5	XM_047432394.1	c.301+2127G>A		intron_variant	Intron 2 of 7		XP_047288350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.301+2127G>A		intron_variant	Intron 2 of 8	1	NM_205850.3	ENSP00000341550.3
SLC24A5	ENST00000449382.2	c.121+2998G>A		intron_variant	Intron 1 of 7	1		ENSP00000389966.2
SLC24A5	ENST00000482911.2	c.*2059G>A		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000453395.1
SLC24A5	ENST00000463289.1	n.61+2127G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18094 AN: 151606 Hom.: 3125 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.00181

Gnomad MID AF: 0.00980

Gnomad NFE AF: 0.000973

Gnomad OTH AF: 0.0821

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.120 AC: 18162 AN: 151728 Hom.: 3143 Cov.: 32 AF XY: 0.118 AC XY: 8753 AN XY: 74150

African (AFR) AF: 0.375 AC: 15522 AN: 41376

American (AMR) AF: 0.116 AC: 1762 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.0772 AC: 400 AN: 5182

South Asian (SAS) AF: 0.0454 AC: 218 AN: 4800

European-Finnish (FIN) AF: 0.00181 AC: 19 AN: 10514

Middle Eastern (MID) AF: 0.0104 AC: 3 AN: 288

European-Non Finnish (NFE) AF: 0.000973 AC: 66 AN: 67858

Other (OTH) AF: 0.0817 AC: 172 AN: 2104

Alfa AF: 0.0192 Hom.: 492

Bravo AF: 0.141

Asia WGS AF: 0.0900 AC: 307 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.36
PhyloP100		0.059
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: rs2433356; hg19: chr15-48416360;