rs3806302

Variant names:

• chr1-180272020-G-A
• rs3806302
• NM_033343.4:c.778+14G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-180272020-G-A
• chr1-180272020-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033343.4(LHX4):​c.778+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LHX4 NM_033343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 5 publications found

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]

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]

LHX4-AS1 (HGNC:40982): (LHX4 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LHX4	NM_033343.4	c.778+14G>A		intron_variant	Intron 5 of 5	ENST00000263726.4	NP_203129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHX4	ENST00000263726.4	c.778+14G>A		intron_variant	Intron 5 of 5	1	NM_033343.4	ENSP00000263726.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457228 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724630

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 44378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25846

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 85880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4994

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110104

Other (OTH) AF: 0.00 AC: 0 AN: 60140

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 723

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		0.38

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

Other links and lift over

dbSNP: rs3806302; hg19: chr1-180241155;