NM_004213.5:c.1368A>G

Variant names:

• chr15-84935179-A-G
• rs2242048
• NM_004213.5:c.1368A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_004213.5(SLC28A1):​c.1368A>G​(p.Gln456Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 1,613,972 control chromosomes in the GnomAD database, including 626,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.89 (61089 hom., cov: 31)
  • Exomes 𝑓: 0.88 (565226 hom.)
• Consequence: SLC28A1 NM_004213.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.228
• Publications: 26 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-84935179-A-G is Benign according to our data. Variant chr15-84935179-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060136.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.228 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 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.1368A>G	p.Gln456Gln	synonymous	Exon 14 of 19	NP_004204.3
	SLC28A1	NM_001287762.2		c.1368A>G	p.Gln456Gln	synonymous	Exon 13 of 18	NP_001274691.1	O00337-1
	SLC28A1	NM_001321722.2		c.1368A>G	p.Gln456Gln	synonymous	Exon 14 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.1368A>G	p.Gln456Gln	synonymous	Exon 14 of 19	ENSP00000378074.1	O00337-1
	SLC28A1	ENST00000286749.3	TSL:1	c.1368A>G	p.Gln456Gln	synonymous	Exon 13 of 18	ENSP00000286749.3	O00337-1
	SLC28A1	ENST00000859184.1		c.1368A>G	p.Gln456Gln	synonymous	Exon 14 of 19	ENSP00000529243.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136043 AN: 152056 Hom.: 61029 Cov.: 31

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.894

GnomAD2 exomes AF: 0.885 AC: 222499 AN: 251446 AF XY: 0.885

Gnomad AFR exome AF: 0.949

Gnomad AMR exome AF: 0.858

Gnomad ASJ exome AF: 0.935

Gnomad EAS exome AF: 0.960

Gnomad FIN exome AF: 0.826

Gnomad NFE exome AF: 0.867

Gnomad OTH exome AF: 0.882

GnomAD4 exome AF: 0.879 AC: 1284588 AN: 1461798 Hom.: 565226 Cov.: 55 AF XY: 0.880 AC XY: 639758 AN XY: 727212

African (AFR) AF: 0.951 AC: 31836 AN: 33480

American (AMR) AF: 0.860 AC: 38474 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 24446 AN: 26134

East Asian (EAS) AF: 0.959 AC: 38068 AN: 39700

South Asian (SAS) AF: 0.929 AC: 80175 AN: 86258

European-Finnish (FIN) AF: 0.828 AC: 44194 AN: 53406

Middle Eastern (MID) AF: 0.918 AC: 5295 AN: 5768

European-Non Finnish (NFE) AF: 0.871 AC: 968157 AN: 1111934

Other (OTH) AF: 0.893 AC: 53943 AN: 60394

GnomAD4 genome AF: 0.895 AC: 136164 AN: 152174 Hom.: 61089 Cov.: 31 AF XY: 0.895 AC XY: 66567 AN XY: 74372

African (AFR) AF: 0.949 AC: 39406 AN: 41544

American (AMR) AF: 0.863 AC: 13191 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3241 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4950 AN: 5180

South Asian (SAS) AF: 0.936 AC: 4509 AN: 4818

European-Finnish (FIN) AF: 0.827 AC: 8722 AN: 10550

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59121 AN: 68018

Other (OTH) AF: 0.895 AC: 1888 AN: 2110

Alfa AF: 0.883 Hom.: 237778

Bravo AF: 0.898

Asia WGS AF: 0.934 AC: 3248 AN: 3478

EpiCase AF: 0.870

EpiControl AF: 0.867

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		-0.23
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: rs2242048; hg19: chr15-85478410; COSMIC: COSV54476614; COSMIC: COSV54476614;