rs6661125

Positions:

• chr1-180257765-A-G
• chr1-180257765-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033343.4(LHX4):​c.249-8627A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,160 control chromosomes in the GnomAD database, including 6,378 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 0.25 (6378 hom., cov: 33)
• Consequence: LHX4 NM_033343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX4	NM_033343.4	c.249-8627A>G		intron_variant		ENST00000263726.4	NP_203129.1
LHX4	XM_011510105.3	c.66-8627A>G		intron_variant			XP_011508407.1
LHX4	XM_011510106.4	c.66-8627A>G		intron_variant			XP_011508408.1
LHX4	XM_011510108.3	c.-28-8438A>G		intron_variant			XP_011508410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX4	ENST00000263726.4	c.249-8627A>G		intron_variant		1	NM_033343.4	ENSP00000263726.2
LHX4	ENST00000561113.1	n.185-8627A>G		intron_variant		2		ENSP00000452783.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37795 AN: 152042 Hom.: 6355 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.249 AC: 37868 AN: 152160 Hom.: 6378 Cov.: 33 AF XY: 0.244 AC XY: 18166 AN XY: 74410

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.224

Alfa AF: 0.168 Hom.: 3276

Bravo AF: 0.253

Asia WGS AF: 0.123 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.61

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: rs6661125; hg19: chr1-180226900;