15-84895080-C-CTTG

Variant names:

• chr15-84895080-C-CTTG
• rs17215836
• NM_004213.5:c.419_420insTGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PM4_Supporting BP6 BA1

The NM_004213.5(SLC28A1):​c.419_420insTGT​(p.Leu140_Lys141insVal) variant causes a disruptive 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.29 (6491 hom., cov: 16)
  • Exomes 𝑓: 0.28 (59925 hom.)
• Consequence: SLC28A1 NM_004213.5 disruptive_inframe_insertion
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.123
• Publications: 7 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 -8 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 VariationId is 3060075.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 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.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 19	NP_004204.3
	SLC28A1	NM_001287762.2		c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 5 of 18	NP_001274691.1	O00337-1
	SLC28A1	NM_001321722.2		c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 19	NP_001308651.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC28A1	ENST00000394573.6	TSL:1 MANE Select	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 19	ENSP00000378074.1	O00337-1
	SLC28A1	ENST00000286749.3	TSL:1	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 5 of 18	ENSP00000286749.3	O00337-1
	SLC28A1	ENST00000338602.6	TSL:1	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 7	ENSP00000341629.2	O00337-2

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

GnomAD2 exomes AF: 0.273 AC: 68628 AN: 250936 AF XY: 0.274

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 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

African (AFR) AF: 0.303 AC: 10153 AN: 33480

American (AMR) AF: 0.215 AC: 9603 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 9658 AN: 26136

East Asian (EAS) AF: 0.196 AC: 7779 AN: 39698

South Asian (SAS) AF: 0.201 AC: 17368 AN: 86258

European-Finnish (FIN) AF: 0.297 AC: 15876 AN: 53410

Middle Eastern (MID) AF: 0.359 AC: 2067 AN: 5762

European-Non Finnish (NFE) AF: 0.292 AC: 324383 AN: 1111942

Other (OTH) AF: 0.294 AC: 17771 AN: 60388

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

African (AFR) AF: 0.299 AC: 12396 AN: 41466

American (AMR) AF: 0.256 AC: 3908 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1230 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1024 AN: 5158

South Asian (SAS) AF: 0.190 AC: 918 AN: 4822

European-Finnish (FIN) AF: 0.291 AC: 3069 AN: 10536

Middle Eastern (MID) AF: 0.385 AC: 110 AN: 286

European-Non Finnish (NFE) AF: 0.302 AC: 20484 AN: 67910

Other (OTH) AF: 0.321 AC: 678 AN: 2110

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

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC28A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12
Mutation Taster		=85/15	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17215836; hg19: chr15-85438311; COSMIC: COSV54476112;