Genetic Variant SLC28A1:p.Leu140_Lys141insVal (chr15-84895080-C-CTTG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PM4_SupportingBP6BA1

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

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.123

Publications

7 publications found

Variant links:

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]

SLC28A1 links:

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ACMG classification

Classification was made for transcript

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC28A1	NM_004213.5 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 19	ENST00000394573.6	NP_004204.3	O00337-1B7Z3L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC28A1	ENST00000394573.6 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 19	1	NM_004213.5	ENSP00000378074.1	O00337-1
SLC28A1	ENST00000286749.3 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 5 of 18	1		ENSP00000286749.3	O00337-1
SLC28A1	ENST00000338602.6 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 6 of 7	1		ENSP00000341629.2	O00337-2
SLC28A1	ENST00000538177.5 link	c.419_420insTGT	p.Leu140_Lys141insVal	disruptive_inframe_insertion	Exon 5 of 15	2		ENSP00000443752.1	B7Z3L6

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44043

AN:

151836

Hom.:

6486

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.282

AC XY:

205109

AN XY:

727208

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

18925

37849

56774

75698

94623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.290

AC:

44071

AN:

151954

Hom.:

6491

Cov.:

AF XY:

0.287

AC XY:

21337

AN XY:

74264

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1643

3286

4930

6573

8216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC28A1-related disorder

Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.12

Mutation Taster

=85/15

polymorphism (auto)

(source)

Splicing

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

Publications

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chr15-84895080-C-CTTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over