1-112956232-CG-CGG

Position:

• chr1-112956232-CG-CGG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The ENST00000429288.2(SLC16A1):​c.-45+606_-45+607insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00995 in 153,310 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (26 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (0 hom.)
• Consequence: SLC16A1 ENST00000429288.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.424

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-112956232-C-CG is Benign according to our data. Variant chr1-112956232-C-CG is described in ClinVar as [Likely_benign]. Clinvar id is 291916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1523/152204) while in subpopulation AFR AF= 0.0339 (1410/41538). AF 95% confidence interval is 0.0325. There are 26 homozygotes in gnomad4. There are 715 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A1	NM_003051.4			upstream_gene_variant		ENST00000369626.8	NP_003042.3
SLC16A1	NM_001166496.2			upstream_gene_variant			NP_001159968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A1	ENST00000429288.2	c.-45+606_-45+607insC		intron_variant		3		ENSP00000397106	P1
SLC16A1	ENST00000679803.1	c.-45+1305_-45+1306insC		intron_variant				ENSP00000505879	P1
SLC16A1	ENST00000369626.8			upstream_gene_variant		1	NM_003051.4	ENSP00000358640	P1
SLC16A1	ENST00000458229.6			upstream_gene_variant		2		ENSP00000416167	P1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1522 AN: 152088 Hom.: 26 Cov.: 31

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00271 AC: 3 AN: 1106 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 608

Gnomad4 AFR exome AF: 0.0167

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0156

GnomAD4 genome AF: 0.0100 AC: 1523 AN: 152204 Hom.: 26 Cov.: 31 AF XY: 0.00961 AC XY: 715 AN XY: 74404

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00662

Bravo AF: 0.0112

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 10, 2016

- -

Hyperinsulinism, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs58047463; hg19: chr1-113498854;