Variant rs1131611 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002653.5(PITX1):c.418C>A(p.Arg140Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.127 in 1,597,336 control chromosomes in the GnomAD database, including 17,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4603 hom., cov: 34)

Exomes 𝑓: 0.12 ( 12805 hom. )

Consequence

PITX1
NM_002653.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.58

Variant links:

Genes affected

PITX1 (HGNC:9004): (paired like homeodomain 1) This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family are involved in organ development and left-right asymmetry. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. [provided by RefSeq, Jul 2008]

PITX1 links:

PITX1 (HGNC:):

PITX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 5-135029306-G-T is Benign according to our data. Variant chr5-135029306-G-T is described in ClinVar as [Benign]. Clinvar id is 285760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-135029306-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITX1	NM_002653.5 linkuse as main transcript	c.418C>A	p.Arg140Arg	synonymous_variant	3/3	ENST00000265340.12	NP_002644.4	P78337X5D9A5
PITX1	XM_047417318.1 linkuse as main transcript	c.520C>A	p.Arg174Arg	synonymous_variant	4/4		XP_047273274.1
PITX1	XM_047417319.1 linkuse as main transcript	c.73C>A	p.Arg25Arg	synonymous_variant	3/3		XP_047273275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PITX1	ENST00000265340.12 linkuse as main transcript	c.418C>A	p.Arg140Arg	synonymous_variant	3/3	1	NM_002653.5	ENSP00000265340.6	P78337
PITX1	ENST00000506438.5 linkuse as main transcript	c.418C>A	p.Arg140Arg	synonymous_variant	4/4	1		ENSP00000427542.1	P78337
PITX1	ENST00000503586.1 linkuse as main transcript	n.540C>A		non_coding_transcript_exon_variant	3/3	3
PITX1	ENST00000504936.1 linkuse as main transcript	n.751C>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30230

AN:

152092

Hom.:

4568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.0671

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0499

Gnomad FIN

AF:

0.0755

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.191

GnomAD3 exomes

AF:

0.123

AC:

28929

AN:

235206

Hom.:

2911

AF XY:

0.113

AC XY:

14357

AN XY:

127284

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.0665

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.0481

Gnomad FIN exome

AF:

0.0807

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.119

AC:

172354

AN:

1445126

Hom.:

12805

Cov.:

AF XY:

0.116

AC XY:

83050

AN XY:

716832

show subpopulations

Gnomad4 AFR exome

AF:

0.427

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.0670

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0492

Gnomad4 FIN exome

AF:

0.0812

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.199

AC:

30338

AN:

152210

Hom.:

4603

Cov.:

AF XY:

0.192

AC XY:

14301

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.0671

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0512

Gnomad4 FIN

AF:

0.0755

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.136

Hom.:

2229

Bravo

AF:

0.221

Asia WGS

AF:

0.0520

AC:

182

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 08, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over