dbSNP rs6872664: PITX1:c.170-400G>A (chr5-135031908-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002653.5(PITX1):c.170-400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 229,816 control chromosomes in the GnomAD database, including 5,215 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 0.20 ( 4603 hom., cov: 33)

Exomes 𝑓: 0.10 ( 612 hom. )

Consequence

PITX1
NM_002653.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.443

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

clubfoot
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
brachydactyly-elbow wrist dysplasia syndrome
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

PITX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002653.5. 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
	PITX1	NM_002653.5	MANE Select	c.170-400G>A		intron	N/A	NP_002644.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PITX1	ENST00000265340.12	TSL:1 MANE Select	c.170-400G>A	intron	N/A	ENSP00000265340.6	P78337
PITX1	ENST00000506438.5	TSL:1	c.170-400G>A	intron	N/A	ENSP00000427542.1	P78337
PITX1	ENST00000507253.5	TSL:3	c.170-400G>A	intron	N/A	ENSP00000422908.1	D6R9U1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30225

AN:

152060

Hom.:

4568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.206

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

GnomAD4 exome

AF:

0.100

AC:

7775

AN:

77638

Hom.:

612

Cov.:

AF XY:

0.0964

AC XY:

3859

AN XY:

40012

show subpopulations

African (AFR)

AF:

0.369

AC:

721

AN:

1956

American (AMR)

AF:

0.191

AC:

791

AN:

4136

Ashkenazi Jewish (ASJ)

AF:

0.0671

AC:

135

AN:

2012

East Asian (EAS)

AF:

0.00

AC:

AN:

4044

South Asian (SAS)

AF:

0.0435

AC:

363

AN:

8346

European-Finnish (FIN)

AF:

0.0766

AC:

267

AN:

3486

Middle Eastern (MID)

AF:

0.0701

AC:

AN:

328

European-Non Finnish (NFE)

AF:

0.102

AC:

5010

AN:

48916

Other (OTH)

AF:

0.105

AC:

465

AN:

4414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

320

641

961

1282

1602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.199

AC:

30333

AN:

152178

Hom.:

4603

Cov.:

AF XY:

0.192

AC XY:

14295

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.424

AC:

17565

AN:

41448

American (AMR)

AF:

0.207

AC:

3163

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0671

AC:

233

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5186

South Asian (SAS)

AF:

0.0511

AC:

247

AN:

4830

European-Finnish (FIN)

AF:

0.0755

AC:

801

AN:

10614

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7869

AN:

68016

Other (OTH)

AF:

0.189

AC:

399

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1109

2219

3328

4438

5547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.172

Hom.:

455

Bravo

AF:

0.221

Asia WGS

AF:

0.0520

AC:

182

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

(source)

DANN

Benign

0.53

PhyloP100

0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over