Variant chr1-180230592-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033343.4(LHX4):c.63T>C(p.Gly21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,613,584 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 48 hom., cov: 31)

Exomes 𝑓: 0.0047 ( 334 hom. )

Consequence

LHX4
NM_033343.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.338

Variant links:

Genes affected

LHX4 (HGNC:21734): (LIM homeobox 4) This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor involved in the control of differentiation and development of the pituitary gland. Mutations in this gene cause combined pituitary hormone deficiency 4. [provided by RefSeq, Dec 2010]

LHX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-180230592-T-C is Benign according to our data. Variant chr1-180230592-T-C is described in ClinVar as [Benign]. Clinvar id is 293858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-180230592-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.338 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LHX4	NM_033343.4 linkuse as main transcript	c.63T>C	p.Gly21=	synonymous_variant	1/6	ENST00000263726.4
LHX4	XM_011510105.3 linkuse as main transcript	c.-108+1679T>C		intron_variant
LHX4	XM_011510106.4 linkuse as main transcript	c.-108+1439T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHX4	ENST00000263726.4 linkuse as main transcript	c.63T>C	p.Gly21=	synonymous_variant	1/6	1	NM_033343.4	P1
LHX4	ENST00000558139.1 linkuse as main transcript	n.295T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00604

AC:

919

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.00763

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.0121

AC:

3022

AN:

250626

Hom.:

146

AF XY:

0.0109

AC XY:

1482

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00489

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.132

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.00887

Gnomad NFE exome

AF:

0.000751

Gnomad OTH exome

AF:

0.00621

GnomAD4 exome

AF:

0.00465

AC:

6800

AN:

1461358

Hom.:

334

Cov.:

AF XY:

0.00454

AC XY:

3302

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00467

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.00370

Gnomad4 FIN exome

AF:

0.00879

Gnomad4 NFE exome

AF:

0.000324

Gnomad4 OTH exome

AF:

0.00861

GnomAD4 genome

AF:

0.00604

AC:

919

AN:

152226

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

492

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.00763

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.00666

Asia WGS

AF:

0.0410

AC:

144

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 05, 2024	- -

Short stature-pituitary and cerebellar defects-small sella turcica syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over