dbSNP rs1477403: LOHAN2:n.202+2049G>A (chr16-73389303-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000554640.5(LOHAN2):n.202+2049G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,088 control chromosomes in the GnomAD database, including 29,539 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 0.62 ( 29539 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

LOHAN2
ENST00000554640.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.240

Publications

5 publications found

Variant links:

Genes affected

LOHAN2 (HGNC:51371): (lncRNA oncogene in head and neck cancer 2)

LOHAN2 links:

ZFHX3 (HGNC:777): (zinc finger homeobox 3) This gene encodes a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The protein has also been shown to negatively regulate c-Myb, and transactivate the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (also known as p21CIP1). This gene is reported to function as a tumor suppressor in several cancers, and sequence variants of this gene are also associated with atrial fibrillation. Multiple transcript variants expressed from alternate promoters and encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ZFHX3 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
syndromic complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Broad Center for Mendelian Genomics
spinocerebellar ataxia type 4
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
epilepsy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ZFHX3 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFHX3	NM_001386735.1 link	c.-808+66700C>T		intron_variant	Intron 3 of 16		NP_001373664.1
LOHAN2	NR_038234.1 link	n.450+2049G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
LOHAN2	ENST00000554640.5 link	n.202+2049G>A	intron_variant	Intron 1 of 1	1
LOHAN2	ENST00000555721.2 link	n.454+2049G>A	intron_variant	Intron 1 of 2	1
ZFHX3	ENST00000641206.2 link	c.-1291+66700C>T	intron_variant	Intron 3 of 17		ENSP00000493252.1

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

93828

AN:

151968

Hom.:

29511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.535

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.648

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.729

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.683

Gnomad OTH

AF:

0.606

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.617

AC:

93895

AN:

152086

Hom.:

29539

Cov.:

AF XY:

0.611

AC XY:

45402

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.567

AC:

23504

AN:

41466

American (AMR)

AF:

0.522

AC:

7973

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.648

AC:

2249

AN:

3470

East Asian (EAS)

AF:

0.434

AC:

2243

AN:

5164

South Asian (SAS)

AF:

0.380

AC:

1829

AN:

4816

European-Finnish (FIN)

AF:

0.729

AC:

7719

AN:

10594

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.683

AC:

46423

AN:

67978

Other (OTH)

AF:

0.611

AC:

1291

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1873

3747

5620

7494

9367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.644

Hom.:

17528

Bravo

AF:

0.603

Asia WGS

AF:

0.423

AC:

1471

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

(source)

DANN

Benign

0.43

PhyloP100

-0.24

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over