1-112912477-G-A

Position:

• chr1-112912477-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003051.4(SLC16A1):​c.*1414C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,082 control chromosomes in the GnomAD database, including 33,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33918 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC16A1 NM_003051.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.376

Genes affected

SLC16A1 (HGNC:10922): (solute carrier family 16 member 1) The protein encoded by this gene is a proton-linked monocarboxylate transporter that catalyzes the movement of many monocarboxylates, such as lactate and pyruvate, across the plasma membrane. Mutations in this gene are associated with erythrocyte lactate transporter defect. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2009]

LOC124904342 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-112912477-G-A is Benign according to our data. Variant chr1-112912477-G-A is described in ClinVar as [Benign]. Clinvar id is 291831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A1	NM_003051.4	c.*1414C>T		3_prime_UTR_variant	5/5	ENST00000369626.8	NP_003042.3
SLC16A1	NM_001166496.2	c.*1414C>T		3_prime_UTR_variant	5/5		NP_001159968.1
SLC16A1	XM_047428789.1	c.*1414C>T		3_prime_UTR_variant	5/5		XP_047284745.1
LOC124904342	XR_007066442.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A1	ENST00000369626.8	c.*1414C>T		3_prime_UTR_variant	5/5	1	NM_003051.4	ENSP00000358640	P1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99419 AN: 151964 Hom.: 33858 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.645

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.655 AC: 99542 AN: 152082 Hom.: 33918 Cov.: 32 AF XY: 0.652 AC XY: 48454 AN XY: 74318

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.649

Alfa AF: 0.589 Hom.: 46197

Bravo AF: 0.662

Asia WGS AF: 0.628 AC: 2183 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Exercise-induced hyperinsulinism Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.084
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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

Publications

LitVar

Other links and lift over

dbSNP: rs7169; hg19: chr1-113455099;