Genetic Variant ENST00000616341.1:n.98+35736G>A (chr17-36900828-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000616341.1(LHX1-DT):n.98+35736G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000616341.1 is not a MANE Select or MANE Plus Clinical transcript for LHX1-DT; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.189 (AC=28,772) in the gnomAD database across 152,138 control chromosomes, including 2,903 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.209. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 2903 hom., cov: 33)

Consequence

LHX1-DT
ENST00000616341.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.331

Publications

5 publications found

Variant links:

Genes affected

LHX1-DT (HGNC:53778): (LHX1 divergent transcript)

LHX1-DT links:

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new If you want to explore the variant's impact on the transcript ENST00000616341.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2087 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000616341.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX1-DT	NR_135671.1		n.98+35736G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX1-DT	ENST00000616341.1	TSL:2	n.98+35736G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28755

AN:

152020

Hom.:

2900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.0131

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.189

AC:

28772

AN:

152138

Hom.:

2903

Cov.:

AF XY:

0.186

AC XY:

13862

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.196

AC:

8116

AN:

41488

American (AMR)

AF:

0.136

AC:

2072

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

571

AN:

3470

East Asian (EAS)

AF:

0.0131

AC:

AN:

5190

South Asian (SAS)

AF:

0.109

AC:

528

AN:

4822

European-Finnish (FIN)

AF:

0.208

AC:

2201

AN:

10582

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14388

AN:

67988

Other (OTH)

AF:

0.193

AC:

407

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1215

2431

3646

4862

6077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.196

Hom.:

3941

Bravo

AF:

0.184

Asia WGS

AF:

0.0750

AC:

261

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0275

AC:

3379

AN:

122656

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0114

AC:

102

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.185

AC:

433

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.66

PhyloP100

-0.33

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over