rs687715

Variant names:

• chr1-75214748-G-A
• rs687715
• NM_001130058.2:c.1729-70C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152697.6(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_152697.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962
• Publications: 7 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152697.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A5	NM_001130058.2	MANE Select	c.1729-70C>T		intron	N/A	NP_001123530.1
	SLC44A5	NM_152697.6		c.1729-70C>T		intron	N/A	NP_689910.2
	SLC44A5	NM_001320283.3		c.1711-70C>T		intron	N/A	NP_001307212.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A5	ENST00000370859.8	TSL:2 MANE Select	c.1729-70C>T		intron	N/A	ENSP00000359896.3
	SLC44A5	ENST00000370855.5	TSL:1	c.1729-70C>T		intron	N/A	ENSP00000359892.5

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

African (AFR) AF: 0.484 AC: 12444 AN: 25690

American (AMR) AF: 0.311 AC: 11107 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 9651 AN: 22248

East Asian (EAS) AF: 0.156 AC: 5760 AN: 36860

South Asian (SAS) AF: 0.411 AC: 29029 AN: 70700

European-Finnish (FIN) AF: 0.351 AC: 16750 AN: 47724

Middle Eastern (MID) AF: 0.367 AC: 1838 AN: 5004

European-Non Finnish (NFE) AF: 0.438 AC: 358109 AN: 816848

Other (OTH) AF: 0.409 AC: 19543 AN: 47818

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

African (AFR) AF: 0.478 AC: 19820 AN: 41444

American (AMR) AF: 0.318 AC: 4855 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1508 AN: 3470

East Asian (EAS) AF: 0.174 AC: 896 AN: 5150

South Asian (SAS) AF: 0.393 AC: 1890 AN: 4814

European-Finnish (FIN) AF: 0.328 AC: 3476 AN: 10586

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29175 AN: 67940

Other (OTH) AF: 0.377 AC: 796 AN: 2114

Alfa AF: 0.435 Hom.: 2492

Bravo AF: 0.412

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.53
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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