rs4652492

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033343.4(LHX4):​c.248+851A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,094 control chromosomes in the GnomAD database, including 19,575 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 0.50 ( 19575 hom., cov: 33)

Consequence

LHX4
NM_033343.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LHX4NM_033343.4 linkuse as main transcriptc.248+851A>G intron_variant ENST00000263726.4 NP_203129.1
LHX4XM_011510105.3 linkuse as main transcriptc.65+851A>G intron_variant XP_011508407.1
LHX4XM_011510106.4 linkuse as main transcriptc.65+851A>G intron_variant XP_011508408.1
LHX4XM_011510108.3 linkuse as main transcriptc.-29+851A>G intron_variant XP_011508410.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LHX4ENST00000263726.4 linkuse as main transcriptc.248+851A>G intron_variant 1 NM_033343.4 ENSP00000263726 P1
LHX4ENST00000561113.1 linkuse as main transcriptc.185+838A>G intron_variant, NMD_transcript_variant 2 ENSP00000452783

Frequencies

GnomAD3 genomes
AF:
0.505
AC:
76705
AN:
151974
Hom.:
19540
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.503
Gnomad AMI
AF:
0.411
Gnomad AMR
AF:
0.487
Gnomad ASJ
AF:
0.460
Gnomad EAS
AF:
0.372
Gnomad SAS
AF:
0.604
Gnomad FIN
AF:
0.504
Gnomad MID
AF:
0.398
Gnomad NFE
AF:
0.517
Gnomad OTH
AF:
0.503
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.505
AC:
76799
AN:
152094
Hom.:
19575
Cov.:
33
AF XY:
0.506
AC XY:
37651
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.503
Gnomad4 AMR
AF:
0.487
Gnomad4 ASJ
AF:
0.460
Gnomad4 EAS
AF:
0.373
Gnomad4 SAS
AF:
0.604
Gnomad4 FIN
AF:
0.504
Gnomad4 NFE
AF:
0.517
Gnomad4 OTH
AF:
0.508
Alfa
AF:
0.506
Hom.:
22479
Bravo
AF:
0.501
Asia WGS
AF:
0.516
AC:
1794
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
9.6
DANN
Benign
0.80

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.

Other links and lift over

dbSNP: rs4652492; hg19: chr1-180218442; API