rs3764895

Variant names:

• chr11-2924715-C-T
• rs3764895
• NM_002555.6:c.1088-295C>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.1088-295C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,138 control chromosomes in the GnomAD database, including 2,157 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 0.15 (2157 hom., cov: 32)
• Consequence: SLC67A1 NM_002555.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 14 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 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.1088-295C>T		intron	N/A	NP_002546.3
	SLC67A1	NM_001315501.2		c.1343-295C>T		intron	N/A	NP_001302430.1
	SLC67A1	NM_183233.3		c.1088-295C>T		intron	N/A	NP_899056.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A18	ENST00000649076.2	MANE Select	c.1088-295C>T		intron	N/A	ENSP00000497561.1
	SLC22A18	ENST00000347936.6	TSL:1	c.1088-295C>T		intron	N/A	ENSP00000307859.2
	SLC22A18	ENST00000380574.5	TSL:1	c.1088-295C>T		intron	N/A	ENSP00000369948.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23368 AN: 152020 Hom.: 2155 Cov.: 32

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.154 AC: 23371 AN: 152138 Hom.: 2157 Cov.: 32 AF XY: 0.160 AC XY: 11871 AN XY: 74364

African (AFR) AF: 0.0679 AC: 2818 AN: 41528

American (AMR) AF: 0.141 AC: 2160 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3472

East Asian (EAS) AF: 0.140 AC: 724 AN: 5164

South Asian (SAS) AF: 0.206 AC: 994 AN: 4820

European-Finnish (FIN) AF: 0.298 AC: 3151 AN: 10568

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12413 AN: 67974

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.172 Hom.: 4336

Bravo AF: 0.138

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.42
PhyloP100		-0.36
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: rs3764895; hg19: chr11-2945945;