chr1-112918054-CAATAAATAAATA-C

Variant names:

• chr1-112918054-CAATAAATAAATA-C
• rs149491709
• NM_003051.4:c.362-22_362-11delTATTTATTTATT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_003051.4(SLC16A1):​c.362-22_362-11delTATTTATTTATT variant causes a intron change. The variant allele was found at a frequency of 0.0181 in 857,606 control chromosomes in the GnomAD database, including 240 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.016 (23 hom., cov: 0)
  • Exomes 𝑓: 0.018 (217 hom.)
• Consequence: SLC16A1 NM_003051.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 3.97
• Publications: 1 publications found

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]

SLC16A1-AS1 (HGNC:49445): (SLC16A1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 1-112918054-CAATAAATAAATA-C is Benign according to our data. Variant chr1-112918054-CAATAAATAAATA-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 212184.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0161 (2322/144598) while in subpopulation NFE AF = 0.0173 (1148/66406). AF 95% confidence interval is 0.0165. There are 23 homozygotes in GnomAd4. There are 1171 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AD,AR,Unknown,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A1	NM_003051.4	MANE Select	c.362-22_362-11delTATTTATTTATT		intron	N/A	NP_003042.3
	SLC16A1	NM_001166496.2		c.362-22_362-11delTATTTATTTATT		intron	N/A	NP_001159968.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A1	ENST00000369626.8	TSL:1 MANE Select	c.362-22_362-11delTATTTATTTATT		intron	N/A	ENSP00000358640.4
	SLC16A1	ENST00000429288.2	TSL:3	c.362-22_362-11delTATTTATTTATT		intron	N/A	ENSP00000397106.2
	SLC16A1	ENST00000443580.6	TSL:3	c.362-22_362-11delTATTTATTTATT		intron	N/A	ENSP00000399104.2

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2319 AN: 144526 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00996

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0244

Gnomad EAS AF: 0.00901

Gnomad SAS AF: 0.00595

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0162

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.00795 AC: 483 AN: 60732 AF XY: 0.00807

Gnomad AFR exome AF: 0.00121

Gnomad AMR exome AF: 0.00453

Gnomad ASJ exome AF: 0.0213

Gnomad EAS exome AF: 0.00420

Gnomad FIN exome AF: 0.0129

Gnomad NFE exome AF: 0.00783

Gnomad OTH exome AF: 0.00954

GnomAD4 exome AF: 0.0185 AC: 13180 AN: 713008 Hom.: 217 AF XY: 0.0181 AC XY: 6543 AN XY: 360876

African (AFR) AF: 0.0123 AC: 180 AN: 14608

American (AMR) AF: 0.0105 AC: 135 AN: 12882

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 299 AN: 14250

East Asian (EAS) AF: 0.00276 AC: 67 AN: 24268

South Asian (SAS) AF: 0.00690 AC: 158 AN: 22910

European-Finnish (FIN) AF: 0.0211 AC: 440 AN: 20864

Middle Eastern (MID) AF: 0.0195 AC: 43 AN: 2204

European-Non Finnish (NFE) AF: 0.0198 AC: 11270 AN: 570374

Other (OTH) AF: 0.0192 AC: 588 AN: 30648

GnomAD4 genome AF: 0.0161 AC: 2322 AN: 144598 Hom.: 23 Cov.: 0 AF XY: 0.0167 AC XY: 1171 AN XY: 70192

African (AFR) AF: 0.0118 AC: 456 AN: 38738

American (AMR) AF: 0.0153 AC: 223 AN: 14534

Ashkenazi Jewish (ASJ) AF: 0.0244 AC: 84 AN: 3438

East Asian (EAS) AF: 0.00883 AC: 44 AN: 4984

South Asian (SAS) AF: 0.00598 AC: 27 AN: 4518

European-Finnish (FIN) AF: 0.0311 AC: 273 AN: 8792

Middle Eastern (MID) AF: 0.0176 AC: 5 AN: 284

European-Non Finnish (NFE) AF: 0.0173 AC: 1148 AN: 66406

Other (OTH) AF: 0.0265 AC: 53 AN: 2000

Alfa AF: 0.00667 Hom.: 967

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 03, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Hyperinsulinism, Dominant Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Feb 22, 2016

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149491709; hg19: chr1-113460676;