chr15-84887738-C-T

Variant names:

• chr15-84887738-C-T
• rs3743162
• NM_004213.5:c.-16-7C>T

Variant summary

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

The NM_004213.5(SLC28A1):​c.-16-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,611,914 control chromosomes in the GnomAD database, including 35,921 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 (2727 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33194 hom.)
• Consequence: SLC28A1 NM_004213.5 splice_region, intron
• Scores: Splicing: ADA: 0.00001670
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 21 publications found

Genes affected

SLC28A1 (HGNC:11001): (solute carrier family 28 member 1) Enables azole transmembrane transporter activity; cytidine transmembrane transporter activity; and uridine transmembrane transporter activity. Involved in azole transmembrane transport; nucleoside transport; and pyrimidine-containing compound transmembrane transport. Located in cytosol; nuclear speck; and plasma 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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A1	NM_004213.5	MANE Select	c.-16-7C>T		splice_region intron	N/A	NP_004204.3
	SLC28A1	NM_001287762.2		c.-16-7C>T		splice_region intron	N/A	NP_001274691.1	O00337-1
	SLC28A1	NM_001321722.2		c.-16-7C>T		splice_region intron	N/A	NP_001308651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A1	ENST00000394573.6	TSL:1 MANE Select	c.-16-7C>T		splice_region intron	N/A	ENSP00000378074.1	O00337-1
	SLC28A1	ENST00000286749.3	TSL:1	c.-16-7C>T		splice_region intron	N/A	ENSP00000286749.3	O00337-1
	SLC28A1	ENST00000338602.6	TSL:1	c.-16-7C>T		splice_region intron	N/A	ENSP00000341629.2	O00337-2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25384 AN: 152060 Hom.: 2732 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.184

GnomAD2 exomes AF: 0.192 AC: 48161 AN: 251242 AF XY: 0.193

Gnomad AFR exome AF: 0.0369

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.118

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.209 AC: 304862 AN: 1459736 Hom.: 33194 Cov.: 31 AF XY: 0.209 AC XY: 151521 AN XY: 726288

African (AFR) AF: 0.0322 AC: 1075 AN: 33424

American (AMR) AF: 0.199 AC: 8883 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 6113 AN: 26118

East Asian (EAS) AF: 0.115 AC: 4555 AN: 39680

South Asian (SAS) AF: 0.145 AC: 12476 AN: 86208

European-Finnish (FIN) AF: 0.249 AC: 13317 AN: 53392

Middle Eastern (MID) AF: 0.244 AC: 1405 AN: 5768

European-Non Finnish (NFE) AF: 0.221 AC: 245214 AN: 1110136

Other (OTH) AF: 0.196 AC: 11824 AN: 60296

GnomAD4 genome AF: 0.167 AC: 25367 AN: 152178 Hom.: 2727 Cov.: 32 AF XY: 0.167 AC XY: 12398 AN XY: 74386

African (AFR) AF: 0.0396 AC: 1646 AN: 41544

American (AMR) AF: 0.198 AC: 3034 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3472

East Asian (EAS) AF: 0.118 AC: 608 AN: 5152

South Asian (SAS) AF: 0.126 AC: 609 AN: 4818

European-Finnish (FIN) AF: 0.253 AC: 2687 AN: 10602

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

European-Non Finnish (NFE) AF: 0.226 AC: 15338 AN: 67976

Other (OTH) AF: 0.182 AC: 383 AN: 2108

Alfa AF: 0.201 Hom.: 9050

Bravo AF: 0.159

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.51
PhyloP100		0.52
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0
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: rs3743162; hg19: chr15-85430969; COSMIC: COSV54476324;