1-75251240-C-T

Position:

• chr1-75251240-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001130058.2(SLC44A5):​c.315G>A​(p.Val105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,611,776 control chromosomes in the GnomAD database, including 428,590 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 0.70 (37533 hom., cov: 31)
  • Exomes 𝑓: 0.73 (391057 hom.)
• Consequence: SLC44A5 NM_001130058.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.983 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC44A5	NM_001130058.2	c.315G>A	p.Val105=	synonymous_variant	7/24	ENST00000370859.8	NP_001123530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A5	ENST00000370859.8	c.315G>A	p.Val105=	synonymous_variant	7/24	2	NM_001130058.2	ENSP00000359896	A1
SLC44A5	ENST00000370855.5	c.315G>A	p.Val105=	synonymous_variant	7/24	1		ENSP00000359892	P4
SLC44A5	ENST00000469525.1	n.599G>A		non_coding_transcript_exon_variant	9/10	5

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105907 AN: 151872 Hom.: 37532 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.705

GnomAD3 exomes AF: 0.746 AC: 187060 AN: 250670 Hom.: 70753 AF XY: 0.744 AC XY: 100808 AN XY: 135430

Gnomad AFR exome AF: 0.562

Gnomad AMR exome AF: 0.837

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.932

Gnomad SAS exome AF: 0.750

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.724

Gnomad OTH exome AF: 0.739

GnomAD4 exome AF: 0.730 AC: 1065555 AN: 1459786 Hom.: 391057 Cov.: 42 AF XY: 0.730 AC XY: 530290 AN XY: 726282

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.826

Gnomad4 ASJ exome AF: 0.688

Gnomad4 EAS exome AF: 0.933

Gnomad4 SAS exome AF: 0.745

Gnomad4 FIN exome AF: 0.726

Gnomad4 NFE exome AF: 0.724

Gnomad4 OTH exome AF: 0.728

GnomAD4 genome AF: 0.697 AC: 105943 AN: 151990 Hom.: 37533 Cov.: 31 AF XY: 0.701 AC XY: 52039 AN XY: 74276

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.733

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.708

Alfa AF: 0.727 Hom.: 100951

Bravo AF: 0.697

Asia WGS AF: 0.826 AC: 2873 AN: 3478

EpiCase AF: 0.729

EpiControl AF: 0.729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.1
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs588098; hg19: chr1-75716925; COSMIC: COSV63758415;