5-33947439-C-A

Variant names:

• chr5-33947439-C-A
• rs250416
• NM_016180.5:c.1157-65G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016180.5(SLC45A2):​c.1157-65G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,409,144 control chromosomes in the GnomAD database, including 9,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (1248 hom., cov: 33)
  • Exomes 𝑓: 0.054 (8489 hom.)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.612
• Publications: 7 publications found

Genes affected

SLC45A2 (HGNC:16472): (solute carrier family 45 member 2) This gene encodes a transporter protein that mediates melanin synthesis. The protein is expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

SLC45A2 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 4

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-33947439-C-A is Benign according to our data. Variant chr5-33947439-C-A is described in ClinVar as Benign. ClinVar VariationId is 1261617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.1157-65G>T		intron_variant	Intron 5 of 6	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.1157-65G>T		intron_variant	Intron 5 of 5		NP_001012527.2
SLC45A2	XM_047417259.1	c.917-65G>T		intron_variant	Intron 5 of 6		XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.1157-65G>T		intron_variant	Intron 5 of 6	1	NM_016180.5	ENSP00000296589.4
SLC45A2	ENST00000382102.7	c.1157-65G>T		intron_variant	Intron 5 of 5	1		ENSP00000371534.3
SLC45A2	ENST00000510600.1	c.632-65G>T		intron_variant	Intron 4 of 4	3		ENSP00000424010.1

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10962 AN: 152178 Hom.: 1234 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0539 AC: 67795 AN: 1256848 Hom.: 8489 AF XY: 0.0574 AC XY: 36488 AN XY: 635146

African (AFR) AF: 0.0620 AC: 1825 AN: 29416

American (AMR) AF: 0.362 AC: 15596 AN: 43082

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 776 AN: 24728

East Asian (EAS) AF: 0.392 AC: 15132 AN: 38606

South Asian (SAS) AF: 0.198 AC: 16183 AN: 81534

European-Finnish (FIN) AF: 0.0136 AC: 717 AN: 52670

Middle Eastern (MID) AF: 0.169 AC: 915 AN: 5402

European-Non Finnish (NFE) AF: 0.0138 AC: 12815 AN: 927772

Other (OTH) AF: 0.0715 AC: 3836 AN: 53638

GnomAD4 genome AF: 0.0722 AC: 10999 AN: 152296 Hom.: 1248 Cov.: 33 AF XY: 0.0798 AC XY: 5946 AN XY: 74468

African (AFR) AF: 0.0611 AC: 2538 AN: 41570

American (AMR) AF: 0.243 AC: 3719 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 107 AN: 3468

East Asian (EAS) AF: 0.418 AC: 2162 AN: 5172

South Asian (SAS) AF: 0.197 AC: 952 AN: 4822

European-Finnish (FIN) AF: 0.0124 AC: 132 AN: 10620

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0166 AC: 1129 AN: 68036

Other (OTH) AF: 0.102 AC: 216 AN: 2116

Alfa AF: 0.0568 Hom.: 1157

Bravo AF: 0.0931

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.55
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs250416; hg19: chr5-33947544; COSMIC: COSV107370967; COSMIC: COSV107370967;