Genetic Variant NM_002305.4:c.-199T>C (chr22-37675504-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002305.4(LGALS1):c.-199T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 541,622 control chromosomes in the GnomAD database, including 28,374 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7061 hom., cov: 32)

Exomes 𝑓: 0.33 ( 21313 hom. )

Consequence

LGALS1
NM_002305.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

17 publications found

Variant links:

Genes affected

LGALS1 (HGNC:6561): (galectin 1) The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. This gene product may act as an autocrine negative growth factor that regulates cell proliferation. [provided by RefSeq, Jul 2008]

LGALS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS1	NM_002305.4 link	c.-199T>C		upstream_gene_variant		ENST00000215909.10	NP_002296.1	P09382A0A384MR27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS1	ENST00000215909.10 link	c.-199T>C		upstream_gene_variant		1	NM_002305.4	ENSP00000215909.5		P09382

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45561

AN:

151912

Hom.:

7069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.222

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.319

GnomAD4 exome

AF:

0.326

AC:

127147

AN:

389592

Hom.:

21313

AF XY:

0.324

AC XY:

66720

AN XY:

205978

show subpopulations

African (AFR)

AF:

0.218

AC:

2057

AN:

9440

American (AMR)

AF:

0.291

AC:

4077

AN:

14028

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

5177

AN:

11992

East Asian (EAS)

AF:

0.291

AC:

7325

AN:

25168

South Asian (SAS)

AF:

0.283

AC:

10816

AN:

38208

European-Finnish (FIN)

AF:

0.309

AC:

8647

AN:

28028

Middle Eastern (MID)

AF:

0.360

AC:

612

AN:

1698

European-Non Finnish (NFE)

AF:

0.340

AC:

81007

AN:

238536

Other (OTH)

AF:

0.330

AC:

7429

AN:

22494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3975

7951

11926

15902

19877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

526

1052

1578

2104

2630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.300

AC:

45553

AN:

152030

Hom.:

7061

Cov.:

AF XY:

0.298

AC XY:

22165

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.221

AC:

9181

AN:

41474

American (AMR)

AF:

0.300

AC:

4585

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1561

AN:

3470

East Asian (EAS)

AF:

0.260

AC:

1343

AN:

5160

South Asian (SAS)

AF:

0.274

AC:

1321

AN:

4818

European-Finnish (FIN)

AF:

0.316

AC:

3345

AN:

10582

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.341

AC:

23149

AN:

67954

Other (OTH)

AF:

0.318

AC:

670

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1623

3246

4869

6492

8115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.309

Hom.:

5042

Bravo

AF:

0.295

Asia WGS

AF:

0.285

AC:

991

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.7

(source)

DANN

Benign

0.75

PhyloP100

-1.3

PromoterAI

0.060

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over