15-84895080-C-CTTG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_004213.5(SLC28A1):c.419_420insTGT(p.Leu140_Lys141insVal) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,752 control chromosomes in the GnomAD database, including 66,416 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6491 hom., cov: 16)
  • Exomes 𝑓: 0.28 (59925 hom.)
• Consequence: SLC28A1 NM_004213.5 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.123

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

Verdict is Benign. Variant got -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004213.5. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 15-84895080-C-CTTG is Benign according to our data. Variant chr15-84895080-C-CTTG is described in ClinVar as [Benign]. Clinvar id is 3060075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC28A1	NM_004213.5	c.419_420insTGT	p.Leu140_Lys141insVal	inframe_insertion	6/19	ENST00000394573.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC28A1	ENST00000394573.6	c.419_420insTGT	p.Leu140_Lys141insVal	inframe_insertion	6/19	1	NM_004213.5	P1
SLC28A1	ENST00000286749.3	c.419_420insTGT	p.Leu140_Lys141insVal	inframe_insertion	5/18	1		P1
SLC28A1	ENST00000338602.6	c.419_420insTGT	p.Leu140_Lys141insVal	inframe_insertion	6/7	1
SLC28A1	ENST00000538177.5	c.419_420insTGT	p.Leu140_Lys141insVal	inframe_insertion	5/15	2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44043 AN: 151836 Hom.: 6486 Cov.: 16

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.322

GnomAD3 exomes AF: 0.273 AC: 68628 AN: 250936 Hom.: 9890 AF XY: 0.274 AC XY: 37253 AN XY: 135718

Gnomad AFR exome AF: 0.297

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.203

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.303

GnomAD4 exome AF: 0.284 AC: 414658 AN: 1461798 Hom.: 59925 Cov.: 35 AF XY: 0.282 AC XY: 205109 AN XY: 727208

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.290 AC: 44071 AN: 151954 Hom.: 6491 Cov.: 16 AF XY: 0.287 AC XY: 21337 AN XY: 74264

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.321

Alfa AF: 0.243 Hom.: 816

Bravo AF: 0.290

Asia WGS AF: 0.226 AC: 787 AN: 3478

EpiCase AF: 0.313

EpiControl AF: 0.317

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC28A1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17215836; hg19: chr15-85438311;