Variant 1-180248265-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033343.4(LHX4):c.77-20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,613,074 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 31 hom. )

Consequence

LHX4
NM_033343.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0340

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=-0.81).

BP6

Variant 1-180248265-C-A is Benign according to our data. Variant chr1-180248265-C-A is described in ClinVar as [Benign]. Clinvar id is 1570824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00174 (265/152364) while in subpopulation SAS AF= 0.0147 (71/4830). AF 95% confidence interval is 0.012. There are 2 homozygotes in gnomad4. There are 136 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 265 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
LHX4	NM_033343.4 linkuse as main transcript	c.77-20C>A	intron_variant	ENST00000263726.4	NP_203129.1	Q969G2A0A0S2Z5S4
LHX4	XM_011510105.3 linkuse as main transcript	c.-107-20C>A	intron_variant		XP_011508407.1
LHX4	XM_011510106.4 linkuse as main transcript	c.-107-20C>A	intron_variant		XP_011508408.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
LHX4	ENST00000263726.4 linkuse as main transcript	c.77-20C>A	intron_variant	1	NM_033343.4	ENSP00000263726.2	Q969G2
LHX4	ENST00000558139.1 linkuse as main transcript	n.309-20C>A	intron_variant	3
LHX4	ENST00000561113.1 linkuse as main transcript	n.-21C>A	upstream_gene_variant	2		ENSP00000452783.1	H0YKF4

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

265

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00332

AC:

824

AN:

248312

Hom.:

AF XY:

0.00409

AC XY:

549

AN XY:

134372

show subpopulations

Gnomad AFR exome

AF:

0.000441

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.00121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.0000930

Gnomad NFE exome

AF:

0.00214

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.00257

AC:

3747

AN:

1460710

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

2167

AN XY:

726532

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00211

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0158

Gnomad4 FIN exome

AF:

0.000282

Gnomad4 NFE exome

AF:

0.00184

Gnomad4 OTH exome

AF:

0.00205

GnomAD4 genome

AF:

0.00174

AC:

265

AN:

152364

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.00130

Asia WGS

AF:

0.00606

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:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 13, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.2

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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