Genetic Variant LALTOP:n.2951A>G (chr2-1546537-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 NR_198951.1(LALTOP):n.2951A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,076 control chromosomes in the GnomAD database, including 35,904 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 0.68 ( 35900 hom., cov: 32)

Exomes 𝑓: 0.64 ( 4 hom. )

Consequence

LALTOP
NR_198951.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

4 publications found

Variant links:

Genes affected

LALTOP (HGNC:58132):

LALTOP links:

ENSG00000231482 (HGNC:):

ENSG00000231482 links:

Genome browser will be placed here

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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LALTOP	NR_198951.1 link	n.2951A>G	non_coding_transcript_exon_variant	Exon 4 of 4
LALTOP	NR_198948.1 link	n.3395+7A>G	splice_region_variant, intron_variant	Intron 5 of 6
LALTOP	NR_198949.1 link	n.3395+7A>G	splice_region_variant, intron_variant	Intron 5 of 6
LALTOP	NR_198950.1 link	n.3046+7A>G	splice_region_variant, intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000231482	ENST00000650512.1 link	n.547+33664A>G	intron_variant	Intron 1 of 3
ENSG00000228613	ENST00000816433.1 link	n.520+7A>G	splice_region_variant, intron_variant	Intron 3 of 3
ENSG00000228613	ENST00000816434.1 link	n.654+7A>G	splice_region_variant, intron_variant	Intron 2 of 2
ENSG00000228613	ENST00000438247.1 link	n.*128A>G	downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

104004

AN:

151936

Hom.:

35841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.781

Gnomad AMI

AF:

0.619

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.682

Gnomad EAS

AF:

0.656

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.651

Gnomad OTH

AF:

0.670

GnomAD4 exome

AF:

0.636

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.700

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000610614), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.342

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.685

AC:

104127

AN:

152054

Hom.:

35900

Cov.:

AF XY:

0.684

AC XY:

50818

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.781

AC:

32390

AN:

41462

American (AMR)

AF:

0.628

AC:

9600

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

2366

AN:

3470

East Asian (EAS)

AF:

0.655

AC:

3370

AN:

5142

South Asian (SAS)

AF:

0.619

AC:

2987

AN:

4822

European-Finnish (FIN)

AF:

0.657

AC:

6955

AN:

10578

Middle Eastern (MID)

AF:

0.637

AC:

186

AN:

292

European-Non Finnish (NFE)

AF:

0.651

AC:

44283

AN:

67986

Other (OTH)

AF:

0.676

AC:

1427

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1722

3445

5167

6890

8612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.664

Hom.:

11938

Bravo

AF:

0.688

Asia WGS

AF:

0.664

AC:

2310

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.5

(source)

DANN

Benign

0.16

PhyloP100

-1.1

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