1-75236989-G-A

Variant names:

• chr1-75236989-G-A
• rs17096508
• NM_001130058.2:c.738C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001130058.2(SLC44A5):​c.738C>T​(p.Leu246Leu) 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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC44A5	NM_001130058.2	c.738C>T	p.Leu246Leu	splice_region_variant, synonymous_variant	Exon 11 of 24	ENST00000370859.8	NP_001123530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A5	ENST00000370859.8	c.738C>T	p.Leu246Leu	splice_region_variant, synonymous_variant	Exon 11 of 24	2	NM_001130058.2	ENSP00000359896.3
SLC44A5	ENST00000370855.5	c.738C>T	p.Leu246Leu	splice_region_variant, synonymous_variant	Exon 11 of 24	1		ENSP00000359892.5

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

GnomAD2 exomes AF: 0.173 AC: 42989 AN: 248286 AF XY: 0.180

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 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

African (AFR) AF: 0.118 AC: 3881 AN: 32754

American (AMR) AF: 0.0842 AC: 3734 AN: 44352

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 5912 AN: 25276

East Asian (EAS) AF: 0.0495 AC: 1944 AN: 39294

South Asian (SAS) AF: 0.182 AC: 15130 AN: 83240

European-Finnish (FIN) AF: 0.186 AC: 9793 AN: 52546

Middle Eastern (MID) AF: 0.222 AC: 1241 AN: 5590

European-Non Finnish (NFE) AF: 0.221 AC: 237434 AN: 1073208

Other (OTH) AF: 0.194 AC: 11295 AN: 58358

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

African (AFR) AF: 0.116 AC: 4811 AN: 41504

American (AMR) AF: 0.112 AC: 1708 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3468

East Asian (EAS) AF: 0.0521 AC: 269 AN: 5164

South Asian (SAS) AF: 0.160 AC: 770 AN: 4814

European-Finnish (FIN) AF: 0.175 AC: 1845 AN: 10554

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14759 AN: 67936

Other (OTH) AF: 0.170 AC: 359 AN: 2110

Alfa AF: 0.204 Hom.: 6535

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
PhyloP100		1.3
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

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