rs443193

Variant names:

• chr11-2915616-G-A
• rs443193
• NM_002555.6:c.537-1006G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-2915616-G-A
• chr11-2915616-G-C
• chr11-2915616-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.537-1006G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,164 control chromosomes in the GnomAD database, including 15,195 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15195 hom., cov: 34)
• Consequence: SLC67A1 NM_002555.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 5 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 (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC67A1	NM_002555.6	c.537-1006G>A		intron_variant	Intron 5 of 10	ENST00000649076.2	NP_002546.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A18	ENST00000649076.2	c.537-1006G>A		intron_variant	Intron 5 of 10		NM_002555.6	ENSP00000497561.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66883 AN: 152046 Hom.: 15188 Cov.: 34

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.440 AC: 66928 AN: 152164 Hom.: 15195 Cov.: 34 AF XY: 0.441 AC XY: 32789 AN XY: 74418

African (AFR) AF: 0.367 AC: 15224 AN: 41520

American (AMR) AF: 0.375 AC: 5744 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1741 AN: 5162

South Asian (SAS) AF: 0.438 AC: 2116 AN: 4826

European-Finnish (FIN) AF: 0.567 AC: 6007 AN: 10594

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33117 AN: 67970

Other (OTH) AF: 0.421 AC: 891 AN: 2114

Alfa AF: 0.461 Hom.: 2796

Bravo AF: 0.422

Asia WGS AF: 0.380 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.51
DANN	Benign	0.70
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs443193; hg19: chr11-2936846;