1-112911949-A-G

Position:

• chr1-112911949-A-G

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.*1942T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,150 control chromosomes in the GnomAD database, including 8,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8794 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: SLC16A1 NM_003051.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0910

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=-0.89).
• BP6: Variant 1-112911949-A-G is Benign according to our data. Variant chr1-112911949-A-G is described in ClinVar as [Benign]. Clinvar id is 291827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A1	NM_003051.4	c.*1942T>C		3_prime_UTR_variant	5/5	ENST00000369626.8	NP_003042.3
LOC124904342	XR_007066442.1	n.2315A>G		non_coding_transcript_exon_variant	2/2
SLC16A1	NM_001166496.2	c.*1942T>C		3_prime_UTR_variant	5/5		NP_001159968.1
SLC16A1	XM_047428789.1	c.*1942T>C		3_prime_UTR_variant	5/5		XP_047284745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A1	ENST00000369626.8	c.*1942T>C		3_prime_UTR_variant	5/5	1	NM_003051.4	ENSP00000358640	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45655 AN: 152024 Hom.: 8765 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.301 AC: 45739 AN: 152142 Hom.: 8794 Cov.: 32 AF XY: 0.294 AC XY: 21900 AN XY: 74386

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0127

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.269

Alfa AF: 0.234 Hom.: 7987

Bravo AF: 0.302

Asia WGS AF: 0.0920 AC: 321 AN: 3478

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 12, 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	-0.89
CADD	Benign	0.98
DANN	Benign	0.75

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: rs9429505; hg19: chr1-113454571;