11-2902596-A-G

Variant names:

• chr11-2902596-A-G
• rs367035
• ENST00000380574.5:c.-255A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PVS1_Supporting BP6_Very_Strong BA1

The NM_001315501.2(SLC67A1):​c.1A>G​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 984,958 control chromosomes in the GnomAD database, including 92,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12613 hom., cov: 34)
  • Exomes 𝑓: 0.44 (79566 hom.)
• Consequence: SLC67A1 NM_001315501.2 start_lost
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.777
• Publications: 48 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]

SLC67A1-AS (HGNC:10965): (SLC22A18 antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 7 codons. Genomic position: 2902614. Lost 0.012 part of the original CDS.
• BP6: Variant 11-2902596-A-G is Benign according to our data. Variant chr11-2902596-A-G is described in ClinVar as Benign. ClinVar VariationId is 768417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001315501.2. 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.-133+232A>G		intron	N/A	NP_002546.3
	SLC67A1	NM_001315501.2		c.1A>G	p.Met1?	start_lost	Exon 1 of 11	NP_001302430.1
	SLC67A1	NM_183233.3		c.-132-618A>G		intron	N/A	NP_899056.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC67A1	ENST00000380574.5	TSL:1	c.-255A>G		5_prime_UTR	Exon 1 of 11	ENSP00000369948.1	Q96BI1
	SLC67A1	ENST00000649076.2	MANE Select	c.-133+232A>G		intron	N/A	ENSP00000497561.1	Q96BI1
	SLC67A1	ENST00000347936.6	TSL:1	c.-132-618A>G		intron	N/A	ENSP00000307859.2	Q96BI1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58622 AN: 151850 Hom.: 12621 Cov.: 34

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.435 AC: 362495 AN: 832992 Hom.: 79566 Cov.: 33 AF XY: 0.434 AC XY: 167042 AN XY: 384682

African (AFR) AF: 0.216 AC: 3402 AN: 15786

American (AMR) AF: 0.490 AC: 482 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 2712 AN: 5154

East Asian (EAS) AF: 0.760 AC: 2761 AN: 3632

South Asian (SAS) AF: 0.480 AC: 7898 AN: 16458

European-Finnish (FIN) AF: 0.325 AC: 91 AN: 280

Middle Eastern (MID) AF: 0.527 AC: 853 AN: 1620

European-Non Finnish (NFE) AF: 0.436 AC: 331793 AN: 761786

Other (OTH) AF: 0.458 AC: 12503 AN: 27292

GnomAD4 genome AF: 0.386 AC: 58625 AN: 151966 Hom.: 12613 Cov.: 34 AF XY: 0.386 AC XY: 28683 AN XY: 74276

African (AFR) AF: 0.223 AC: 9267 AN: 41486

American (AMR) AF: 0.498 AC: 7617 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1816 AN: 3472

East Asian (EAS) AF: 0.759 AC: 3910 AN: 5152

South Asian (SAS) AF: 0.484 AC: 2332 AN: 4818

European-Finnish (FIN) AF: 0.326 AC: 3424 AN: 10508

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28697 AN: 67934

Other (OTH) AF: 0.456 AC: 964 AN: 2112

Alfa AF: 0.425 Hom.: 57262

Bravo AF: 0.396

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.65
PhyloP100		-0.78
PromoterAI		-0.18	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs367035; hg19: chr11-2923826;