Genetic Variant SLC24A5:c.301+736C>T (chr15-48122772-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_205850.3(SLC24A5):c.301+736C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,144 control chromosomes in the GnomAD database, including 7,788 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 ( 7788 hom., cov: 32)

Exomes 𝑓: 0.019 ( 0 hom. )

Consequence

SLC24A5
NM_205850.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.505

Publications

13 publications found

Variant links:

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)

SLC24A5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A5	NM_205850.3 link	c.301+736C>T		intron_variant	Intron 2 of 8	ENST00000341459.8	NP_995322.1	Q71RS6-1
SLC24A5	XM_047432394.1 link	c.301+736C>T		intron_variant	Intron 2 of 7		XP_047288350.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC24A5	ENST00000341459.8 link	c.301+736C>T	intron_variant	Intron 2 of 8	1	NM_205850.3	ENSP00000341550.3	Q71RS6-1
SLC24A5	ENST00000449382.2 link	c.121+1607C>T	intron_variant	Intron 1 of 7	1		ENSP00000389966.2	Q71RS6-2
SLC24A5	ENST00000482911.2 link	c.*668C>T	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000453395.1	H0YLZ0
SLC24A5	ENST00000463289.1 link	n.61+736C>T	intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29709

AN:

151974

Hom.:

7757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.566

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.00415

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.155

GnomAD4 exome

AF:

0.0192

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.196

AC:

29801

AN:

152092

Hom.:

7788

Cov.:

AF XY:

0.196

AC XY:

14612

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.566

AC:

23456

AN:

41412

American (AMR)

AF:

0.169

AC:

2575

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.474

AC:

2454

AN:

5174

South Asian (SAS)

AF:

0.162

AC:

779

AN:

4820

European-Finnish (FIN)

AF:

0.00415

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00210

AC:

143

AN:

68018

Other (OTH)

AF:

0.163

AC:

345

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

719

1438

2158

2877

3596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.101

Hom.:

6457

Bravo

AF:

0.226

Asia WGS

AF:

0.399

AC:

1380

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

(source)

DANN

Benign

0.23

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over