rs78838117

Variant names:

• chr11-2909210-G-A
• rs78838117
• NM_002555.6:c.257G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-2909210-G-A
• chr11-2909210-G-T

Variant summary

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

The NM_002555.6(SLC67A1):​c.257G>A​(p.Arg86His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,536,602 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0034 (17 hom., cov: 35)
  • Exomes 𝑓: 0.0025 (97 hom.)
• Consequence: SLC67A1 NM_002555.6 missense
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:1 B:1
• Conservation: PhyloP100: -0.443
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030741394).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0507 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC67A1	NM_002555.6	MANE Select	c.257G>A	p.Arg86His	missense	Exon 4 of 11	NP_002546.3
	SLC67A1	NM_001315501.2		c.512G>A	p.Arg171His	missense	Exon 4 of 11	NP_001302430.1
	SLC67A1	NM_183233.3		c.257G>A	p.Arg86His	missense	Exon 4 of 11	NP_899056.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC67A1	ENST00000649076.2	MANE Select	c.257G>A	p.Arg86His	missense	Exon 4 of 11	ENSP00000497561.1	Q96BI1
	SLC67A1	ENST00000347936.6	TSL:1	c.257G>A	p.Arg86His	missense	Exon 4 of 11	ENSP00000307859.2	Q96BI1
	SLC67A1	ENST00000380574.5	TSL:1	c.257G>A	p.Arg86His	missense	Exon 4 of 11	ENSP00000369948.1	Q96BI1

Frequencies

GnomAD3 genomes AF: 0.00342 AC: 521 AN: 152194 Hom.: 17 Cov.: 35

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0560

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.0144 AC: 1958 AN: 135996 AF XY: 0.0120

Gnomad AFR exome AF: 0.000662

Gnomad AMR exome AF: 0.0428

Gnomad ASJ exome AF: 0.000642

Gnomad EAS exome AF: 0.0699

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000750

Gnomad OTH exome AF: 0.00772

GnomAD4 exome AF: 0.00247 AC: 3417 AN: 1384292 Hom.: 97 Cov.: 36 AF XY: 0.00235 AC XY: 1604 AN XY: 683808

African (AFR) AF: 0.000260 AC: 8 AN: 30820

American (AMR) AF: 0.0345 AC: 1256 AN: 36406

Ashkenazi Jewish (ASJ) AF: 0.000323 AC: 8 AN: 24768

East Asian (EAS) AF: 0.0462 AC: 1669 AN: 36102

South Asian (SAS) AF: 0.00205 AC: 161 AN: 78584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34756

Middle Eastern (MID) AF: 0.000191 AC: 1 AN: 5246

European-Non Finnish (NFE) AF: 0.0000454 AC: 49 AN: 1079902

Other (OTH) AF: 0.00459 AC: 265 AN: 57708

GnomAD4 genome AF: 0.00343 AC: 522 AN: 152310 Hom.: 17 Cov.: 35 AF XY: 0.00395 AC XY: 294 AN XY: 74480

African (AFR) AF: 0.000433 AC: 18 AN: 41572

American (AMR) AF: 0.0110 AC: 169 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.0560 AC: 289 AN: 5162

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68018

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.00145 Hom.: 1

Bravo AF: 0.00530

ExAC AF: 0.00795 AC: 848

Asia WGS AF: 0.0370 AC: 128 AN: 3476

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Rhabdomyosarcoma, somatic (1)
-	-	1	SLC22A18-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.2
DANN	Benign	0.94
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.98	L
PhyloP100		-0.44
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.82	N
REVEL	Benign	0.028
Sift	Benign	0.52	T
Sift4G	Benign	0.56	T
Polyphen		0.11	B
Vest4		0.055
MPC		0.21
ClinPred		0.0040	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.036
gMVP		0.14
Mutation Taster		=87/13	disease causing (ClinVar)

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: rs78838117; hg19: chr11-2930440;