rs3806302

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_033343.4(LHX4):​c.778+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,608,636 control chromosomes in the GnomAD database, including 7,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (841 hom., cov: 31)
  • Exomes 𝑓: 0.086 (6844 hom.)
• Consequence: LHX4 NM_033343.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-180272020-G-T is Benign according to our data. Variant chr1-180272020-G-T is described in ClinVar as Benign. ClinVar VariationId is 262224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX4	NM_033343.4	MANE Select	c.778+14G>T		intron	N/A	NP_203129.1	A0A0S2Z5S4
	LHX4-AS1	NR_037642.1		n.349-49C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHX4	ENST00000263726.4	TSL:1 MANE Select	c.778+14G>T		intron	N/A	ENSP00000263726.2	Q969G2
	LHX4	ENST00000930099.1		c.763+14G>T		intron	N/A	ENSP00000600158.1
	ACBD6	ENST00000642319.1		c.*1254-49C>A		intron	N/A	ENSP00000495710.1	Q9BR61

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13800 AN: 151562 Hom.: 832 Cov.: 31

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.0549

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.0718

GnomAD2 exomes AF: 0.104 AC: 25553 AN: 246848 AF XY: 0.0936

Gnomad AFR exome AF: 0.0992

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.0368

Gnomad FIN exome AF: 0.0660

Gnomad NFE exome AF: 0.0794

Gnomad OTH exome AF: 0.0881

GnomAD4 exome AF: 0.0857 AC: 124789 AN: 1456954 Hom.: 6844 Cov.: 32 AF XY: 0.0837 AC XY: 60619 AN XY: 724512

African (AFR) AF: 0.0942 AC: 3140 AN: 33348

American (AMR) AF: 0.298 AC: 13210 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.0134 AC: 346 AN: 25844

East Asian (EAS) AF: 0.0522 AC: 2070 AN: 39664

South Asian (SAS) AF: 0.0594 AC: 5098 AN: 85872

European-Finnish (FIN) AF: 0.0673 AC: 3559 AN: 52856

Middle Eastern (MID) AF: 0.0342 AC: 171 AN: 4994

European-Non Finnish (NFE) AF: 0.0835 AC: 92698 AN: 1109902

Other (OTH) AF: 0.0748 AC: 4497 AN: 60130

GnomAD4 genome AF: 0.0912 AC: 13827 AN: 151682 Hom.: 841 Cov.: 31 AF XY: 0.0923 AC XY: 6834 AN XY: 74066

African (AFR) AF: 0.0950 AC: 3933 AN: 41384

American (AMR) AF: 0.187 AC: 2852 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.0434 AC: 221 AN: 5098

South Asian (SAS) AF: 0.0553 AC: 260 AN: 4698

European-Finnish (FIN) AF: 0.0690 AC: 727 AN: 10534

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0823 AC: 5590 AN: 67934

Other (OTH) AF: 0.0711 AC: 150 AN: 2110

Alfa AF: 0.0778 Hom.: 723

Bravo AF: 0.103

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Short stature-pituitary and cerebellar defects-small sella turcica syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;