1-180248017-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033343.4(LHX4):c.77-268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,158 control chromosomes in the GnomAD database, including 3,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3200 hom., cov: 33)
• Consequence: LHX4 NM_033343.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.483

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-180248017-C-T is Benign according to our data. Variant chr1-180248017-C-T is described in ClinVar as [Benign]. Clinvar id is 1226843.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHX4	NM_033343.4	c.77-268C>T		intron_variant		ENST00000263726.4
LHX4	XM_011510105.3	c.-107-268C>T		intron_variant
LHX4	XM_011510106.4	c.-107-268C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHX4	ENST00000263726.4	c.77-268C>T		intron_variant		1	NM_033343.4	P1
LHX4	ENST00000558139.1	n.309-268C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30061 AN: 152040 Hom.: 3196 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.172

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.198 AC: 30092 AN: 152158 Hom.: 3200 Cov.: 33 AF XY: 0.194 AC XY: 14408 AN XY: 74388

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.170

Alfa AF: 0.187 Hom.: 353

Bravo AF: 0.197

Asia WGS AF: 0.117 AC: 404 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.0
Dann	Benign	0.63

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

Other links and lift over

dbSNP: rs61809133; hg19: chr1-180217152;