Variant chr1-180230410-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033343.4(LHX4):c.-120C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 857,602 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 104 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 55 hom. )

Consequence

LHX4
NM_033343.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.372

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:

LHX4 (HGNC:):

LHX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-180230410-C-T is Benign according to our data. Variant chr1-180230410-C-T is described in ClinVar as [Benign]. Clinvar id is 293856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
LHX4	NM_033343.4 linkuse as main transcript	c.-120C>T	5_prime_UTR_variant	1/6	ENST00000263726.4	NP_203129.1	Q969G2A0A0S2Z5S4
LHX4	XM_011510105.3 linkuse as main transcript	c.-108+1497C>T	intron_variant			XP_011508407.1
LHX4	XM_011510106.4 linkuse as main transcript	c.-108+1257C>T	intron_variant			XP_011508408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX4	ENST00000263726 linkuse as main transcript	c.-120C>T		5_prime_UTR_variant	1/6	1	NM_033343.4	ENSP00000263726.2		Q969G2
LHX4	ENST00000558139.1 linkuse as main transcript	n.113C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3252

AN:

151890

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0211

GnomAD4 exome

AF:

0.00292

AC:

2059

AN:

705598

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

868

AN XY:

371554

show subpopulations

Gnomad4 AFR exome

AF:

0.0740

Gnomad4 AMR exome

AF:

0.00551

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000123

Gnomad4 FIN exome

AF:

0.0000275

Gnomad4 NFE exome

AF:

0.000455

Gnomad4 OTH exome

AF:

0.00782

GnomAD4 genome

AF:

0.0214

AC:

3252

AN:

152004

Hom.:

104

Cov.:

AF XY:

0.0207

AC XY:

1535

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0722

Gnomad4 AMR

AF:

0.0113

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00546

Hom.:

Bravo

AF:

0.0246

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.78

CADD

Benign

DANN

Benign

0.81

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