11-2903361-G-A

Variant names:

• chr11-2903361-G-A
• rs1048046
• NM_002555.6:c.16G>A

Variant summary

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

The NM_002555.6(SLC67A1):​c.16G>A​(p.Ala6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,612,492 control chromosomes in the GnomAD database, including 27,823 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.20 (3441 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24382 hom.)
• Consequence: SLC67A1 NM_002555.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474
• Publications: 30 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=0.015569568).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002555.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC67A1	NM_002555.6	MANE Select	c.16G>A	p.Ala6Thr	missense	Exon 2 of 11	NP_002546.3
	SLC67A1	NM_001315501.2		c.271G>A	p.Ala91Thr	missense	Exon 2 of 11	NP_001302430.1
	SLC67A1	NM_183233.3		c.16G>A	p.Ala6Thr	missense	Exon 2 of 11	NP_899056.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A18	ENST00000649076.2	MANE Select	c.16G>A	p.Ala6Thr	missense	Exon 2 of 11	ENSP00000497561.1
	SLC22A18	ENST00000347936.6	TSL:1	c.16G>A	p.Ala6Thr	missense	Exon 2 of 11	ENSP00000307859.2
	SLC22A18	ENST00000380574.5	TSL:1	c.16G>A	p.Ala6Thr	missense	Exon 2 of 11	ENSP00000369948.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30178 AN: 151926 Hom.: 3432 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00290

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.172 AC: 42833 AN: 249634 AF XY: 0.173

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0859

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.00152

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.176 AC: 256728 AN: 1460448 Hom.: 24382 Cov.: 32 AF XY: 0.177 AC XY: 128275 AN XY: 726522

African (AFR) AF: 0.280 AC: 9360 AN: 33472

American (AMR) AF: 0.0920 AC: 4112 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4314 AN: 26124

East Asian (EAS) AF: 0.00123 AC: 49 AN: 39700

South Asian (SAS) AF: 0.184 AC: 15902 AN: 86250

European-Finnish (FIN) AF: 0.302 AC: 15819 AN: 52354

Middle Eastern (MID) AF: 0.150 AC: 866 AN: 5764

European-Non Finnish (NFE) AF: 0.176 AC: 195722 AN: 1111704

Other (OTH) AF: 0.175 AC: 10584 AN: 60364

GnomAD4 genome AF: 0.199 AC: 30213 AN: 152044 Hom.: 3441 Cov.: 33 AF XY: 0.201 AC XY: 14974 AN XY: 74324

African (AFR) AF: 0.265 AC: 10969 AN: 41446

American (AMR) AF: 0.120 AC: 1838 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3470

East Asian (EAS) AF: 0.00291 AC: 15 AN: 5158

South Asian (SAS) AF: 0.183 AC: 883 AN: 4826

European-Finnish (FIN) AF: 0.307 AC: 3257 AN: 10592

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12125 AN: 67930

Other (OTH) AF: 0.175 AC: 371 AN: 2116

Alfa AF: 0.180 Hom.: 3538

Bravo AF: 0.188

TwinsUK AF: 0.170 AC: 631

ALSPAC AF: 0.181 AC: 699

ESP6500AA AF: 0.264 AC: 1163

ESP6500EA AF: 0.180 AC: 1545

ExAC AF: 0.176 AC: 21406

Asia WGS AF: 0.113 AC: 395 AN: 3478

EpiCase AF: 0.174

EpiControl AF: 0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00063	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.47
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.048
Sift	Benign	0.15	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.028	B
Vest4		0.032
MPC		0.17
ClinPred		0.0056	T
GERP RS		0.67
PromoterAI		0.0048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.39
Mutation Taster		=99/1	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: rs1048046; hg19: chr11-2924591; COSMIC: COSV56539462; COSMIC: COSV56539462;