Variant 1-180271617-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.606+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,546,794 control chromosomes in the GnomAD database, including 185,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 14042 hom., cov: 30)

Exomes 𝑓: 0.49 ( 171449 hom. )

Consequence

LHX4
NM_033343.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.52

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:

ACBD6 (HGNC:23339): (acyl-CoA binding domain containing 6) Predicted to enable fatty-acyl-CoA binding activity and lipid binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACBD6 links:

ACBD6 (HGNC:):

ACBD6 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=-0.88).

BP6

Variant 1-180271617-C-T is Benign according to our data. Variant chr1-180271617-C-T is described in ClinVar as [Benign]. Clinvar id is 1266198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX4	NM_033343.4 linkuse as main transcript	c.606+83C>T		intron_variant		ENST00000263726.4	NP_203129.1	Q969G2A0A0S2Z5S4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX4	ENST00000263726.4 linkuse as main transcript	c.606+83C>T		intron_variant		1	NM_033343.4	ENSP00000263726.2		Q969G2

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60619

AN:

151592

Hom.:

14049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.563

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.410

GnomAD4 exome

AF:

0.489

AC:

682764

AN:

1395084

Hom.:

171449

Cov.:

AF XY:

0.495

AC XY:

344604

AN XY:

696366

show subpopulations

Gnomad4 AFR exome

AF:

0.155

Gnomad4 AMR exome

AF:

0.264

Gnomad4 ASJ exome

AF:

0.488

Gnomad4 EAS exome

AF:

0.552

Gnomad4 SAS exome

AF:

0.586

Gnomad4 FIN exome

AF:

0.543

Gnomad4 NFE exome

AF:

0.497

Gnomad4 OTH exome

AF:

0.480

GnomAD4 genome

AF:

0.399

AC:

60598

AN:

151710

Hom.:

14042

Cov.:

AF XY:

0.405

AC XY:

29997

AN XY:

74094

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.491

Gnomad4 EAS

AF:

0.564

Gnomad4 SAS

AF:

0.591

Gnomad4 FIN

AF:

0.549

Gnomad4 NFE

AF:

0.499

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.480

Hom.:

17857

Bravo

AF:

0.371

Asia WGS

AF:

0.491

AC:

1704

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	GeneDx	Nov 12, 2018	- -
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

-0.88

CADD

Benign

0.17

DANN

Benign

0.58

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