rs1048047

Variant names:

• chr11-2903380-G-A
• rs1048047
• NM_002555.6:c.35G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-2903380-G-A
• chr11-2903380-G-C

Variant summary

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

The NM_002555.6(SLC67A1):​c.35G>A​(p.Arg12Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,612,552 control chromosomes in the GnomAD database, including 281,386 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (24570 hom., cov: 32)
  • Exomes 𝑓: 0.59 (256816 hom.)
• Consequence: SLC67A1 NM_002555.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 48 publications found

Genes affected

SLC67A1 (HGNC:10964): (solute carrier family 22 member 18) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015]

SLC22A18AS (HGNC:10965): (SLC22A18 antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3087936E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC67A1	NM_002555.6	c.35G>A	p.Arg12Gln	missense_variant	Exon 2 of 11	ENST00000649076.2	NP_002546.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A18	ENST00000649076.2	c.35G>A	p.Arg12Gln	missense_variant	Exon 2 of 11		NM_002555.6	ENSP00000497561.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85430 AN: 151834 Hom.: 24567 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.598

GnomAD2 exomes AF: 0.613 AC: 153048 AN: 249804 AF XY: 0.614

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.642

Gnomad ASJ exome AF: 0.630

Gnomad EAS exome AF: 0.778

Gnomad FIN exome AF: 0.620

Gnomad NFE exome AF: 0.582

Gnomad OTH exome AF: 0.613

GnomAD4 exome AF: 0.591 AC: 863728 AN: 1460600 Hom.: 256816 Cov.: 55 AF XY: 0.593 AC XY: 431139 AN XY: 726598

African (AFR) AF: 0.482 AC: 16144 AN: 33474

American (AMR) AF: 0.633 AC: 28324 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 16520 AN: 26128

East Asian (EAS) AF: 0.727 AC: 28875 AN: 39700

South Asian (SAS) AF: 0.654 AC: 56375 AN: 86250

European-Finnish (FIN) AF: 0.621 AC: 32565 AN: 52430

Middle Eastern (MID) AF: 0.651 AC: 3756 AN: 5766

European-Non Finnish (NFE) AF: 0.580 AC: 644501 AN: 1111768

Other (OTH) AF: 0.607 AC: 36668 AN: 60372

GnomAD4 genome AF: 0.562 AC: 85469 AN: 151952 Hom.: 24570 Cov.: 32 AF XY: 0.568 AC XY: 42176 AN XY: 74292

African (AFR) AF: 0.473 AC: 19590 AN: 41414

American (AMR) AF: 0.594 AC: 9090 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2205 AN: 3468

East Asian (EAS) AF: 0.761 AC: 3924 AN: 5156

South Asian (SAS) AF: 0.656 AC: 3156 AN: 4812

European-Finnish (FIN) AF: 0.626 AC: 6620 AN: 10582

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38886 AN: 67906

Other (OTH) AF: 0.595 AC: 1258 AN: 2116

Alfa AF: 0.581 Hom.: 47487

Bravo AF: 0.562

TwinsUK AF: 0.562 AC: 2085

ALSPAC AF: 0.572 AC: 2206

ESP6500AA AF: 0.478 AC: 2107

ESP6500EA AF: 0.575 AC: 4948

ExAC AF: 0.607 AC: 73622

Asia WGS AF: 0.661 AC: 2297 AN: 3478

EpiCase AF: 0.589

EpiControl AF: 0.597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.4
DANN	Benign	0.85
DEOGEN2	Benign	0.0017	T;T;T;.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.38	.;.;.;T;T;T
MetaRNN	Benign	0.0000013	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.6	N;N;N;.;N;.
PhyloP100		0.0080
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.93	N;N;.;N;N;N
REVEL	Benign	0.027
Sift	Benign	1.0	T;T;.;T;T;T
Sift4G	Benign	1.0	T;T;.;T;T;T
Polyphen		0.0010	B;B;B;B;B;.
Vest4		0.015
MPC		0.20
ClinPred		0.00014	T
GERP RS		-1.5
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.015
gMVP		0.16
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: rs1048047; hg19: chr11-2924610; COSMIC: COSV56539474;