rs687715

chr1-75214748-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130058.2(SLC44A5):c.1729-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,260,590 control chromosomes in the GnomAD database, including 113,822 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 0.41 (13478 hom., cov: 32)
  • Exomes 𝑓: 0.42 (100344 hom.)
• Consequence: SLC44A5 NM_001130058.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A5	NM_001130058.2	c.1729-70C>T		intron_variant		ENST00000370859.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A5	ENST00000370859.8	c.1729-70C>T		intron_variant		2	NM_001130058.2	A1
SLC44A5	ENST00000370855.5	c.1729-70C>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62858 AN: 151884 Hom.: 13469 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.419 AC: 464231 AN: 1108588 Hom.: 100344 AF XY: 0.419 AC XY: 233910 AN XY: 558578

Gnomad4 AFR exome AF: 0.484

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.414 AC: 62909 AN: 152002 Hom.: 13478 Cov.: 32 AF XY: 0.403 AC XY: 29979 AN XY: 74298

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.377

Alfa AF: 0.433 Hom.: 2398

Bravo AF: 0.412

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.6
Dann	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs687715; hg19: chr1-75680433; COSMIC: COSV63760407;