rs17096508

Positions:

• chr1-75236989-G-A
• chr1-75236989-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001130058.2(SLC44A5):​c.738C>T​(p.Leu246=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,566,620 control chromosomes in the GnomAD database, including 34,153 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2440 hom., cov: 32)
  • Exomes 𝑓: 0.21 (31713 hom.)
• Consequence: SLC44A5 NM_001130058.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.4096
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

Genes affected

SLC44A5 (HGNC:28524): (solute carrier family 44 member 5) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A5	NM_001130058.2	c.738C>T	p.Leu246=	splice_region_variant, synonymous_variant	11/24	ENST00000370859.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A5	ENST00000370859.8	c.738C>T	p.Leu246=	splice_region_variant, synonymous_variant	11/24	2	NM_001130058.2	A1
SLC44A5	ENST00000370855.5	c.738C>T	p.Leu246=	splice_region_variant, synonymous_variant	11/24	1		P4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25705 AN: 151884 Hom.: 2438 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0518

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.172

GnomAD3 exomes AF: 0.173 AC: 42989 AN: 248286 Hom.: 4249 AF XY: 0.180 AC XY: 24158 AN XY: 134238

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.0793

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.0549

Gnomad SAS exome AF: 0.180

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.205 AC: 290364 AN: 1414618 Hom.: 31713 Cov.: 25 AF XY: 0.206 AC XY: 144822 AN XY: 704526

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0842

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.0495

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.169 AC: 25712 AN: 152002 Hom.: 2440 Cov.: 32 AF XY: 0.165 AC XY: 12237 AN XY: 74300

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0521

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.170

Alfa AF: 0.207 Hom.: 5543

Bravo AF: 0.160

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.41
dbscSNV1_RF	Benign	0.49
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

Publications

LitVar

Other links and lift over

dbSNP: rs17096508; hg19: chr1-75702674; COSMIC: COSV63760516;