chr11-2909627-G-C

Variant names:

• chr11-2909627-G-C
• rs1177756256
• NM_002555.6:c.453G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_002555.6(SLC67A1):​c.453G>C​(p.Ala151Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,381,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: SLC67A1 NM_002555.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.848
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-2909627-G-C is Benign according to our data. Variant chr11-2909627-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2641509.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.848 with no splicing effect.

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.453G>C	p.Ala151Ala	synonymous	Exon 5 of 11	NP_002546.3
	SLC67A1	NM_001315501.2		c.708G>C	p.Ala236Ala	synonymous	Exon 5 of 11	NP_001302430.1
	SLC67A1	NM_183233.3		c.453G>C	p.Ala151Ala	synonymous	Exon 5 of 11	NP_899056.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC67A1	ENST00000649076.2	MANE Select	c.453G>C	p.Ala151Ala	synonymous	Exon 5 of 11	ENSP00000497561.1	Q96BI1
	SLC67A1	ENST00000347936.6	TSL:1	c.453G>C	p.Ala151Ala	synonymous	Exon 5 of 11	ENSP00000307859.2	Q96BI1
	SLC67A1	ENST00000380574.5	TSL:1	c.453G>C	p.Ala151Ala	synonymous	Exon 5 of 11	ENSP00000369948.1	Q96BI1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000788 AC: 1 AN: 126930 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000259

GnomAD4 exome AF: 0.00000579 AC: 8 AN: 1381008 Hom.: 0 Cov.: 35 AF XY: 0.00000440 AC XY: 3 AN XY: 681660

African (AFR) AF: 0.00 AC: 0 AN: 30484

American (AMR) AF: 0.00 AC: 0 AN: 35446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24870

East Asian (EAS) AF: 0.00 AC: 0 AN: 35088

South Asian (SAS) AF: 0.00 AC: 0 AN: 78772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36784

Middle Eastern (MID) AF: 0.000195 AC: 1 AN: 5134

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1076810

Other (OTH) AF: 0.0000868 AC: 5 AN: 57620

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.3
DANN	Benign	0.67
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1177756256; hg19: chr11-2930857;