chr1-180248057-C-A

Position:

• chr1-180248057-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033343.4(LHX4):​c.77-228C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,228 control chromosomes in the GnomAD database, including 2,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.18 (2692 hom., cov: 33)
• Consequence: LHX4 NM_033343.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.234

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-180248057-C-A is Benign according to our data. Variant chr1-180248057-C-A is described in ClinVar as [Benign]. Clinvar id is 1230908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHX4	NM_033343.4	c.77-228C>A		intron_variant		ENST00000263726.4
LHX4	XM_011510105.3	c.-107-228C>A		intron_variant
LHX4	XM_011510106.4	c.-107-228C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHX4	ENST00000263726.4	c.77-228C>A		intron_variant		1	NM_033343.4	P1
LHX4	ENST00000558139.1	n.309-228C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27881 AN: 152110 Hom.: 2691 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.183 AC: 27907 AN: 152228 Hom.: 2692 Cov.: 33 AF XY: 0.180 AC XY: 13369 AN XY: 74428

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.0821

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.159

Alfa AF: 0.187 Hom.: 341

Bravo AF: 0.181

Asia WGS AF: 0.113 AC: 390 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	-0.75
CADD	Benign	3.3
DANN	Benign	0.89

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: rs61809134; hg19: chr1-180217192;