dbSNP rs113986847: PITX1:c.-221G>T (chr5-135034102-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002653.5(PITX1):c.-221G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 165,788 control chromosomes in the GnomAD database, including 396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.052 ( 331 hom., cov: 31)

Exomes 𝑓: 0.083 ( 65 hom. )

Consequence

PITX1
NM_002653.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.45

Publications

0 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 links:

PITX1-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

PITX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 5-135034102-C-A is Benign according to our data. Variant chr5-135034102-C-A is described in ClinVar as Benign. ClinVar VariationId is 1274487.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0686 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.-221G>T		5_prime_UTR	Exon 1 of 3	NP_002644.4
	PITX1-AS1	NR_161235.1		n.267+562C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PITX1	ENST00000265340.12	TSL:1 MANE Select	c.-221G>T	5_prime_UTR	Exon 1 of 3	ENSP00000265340.6	P78337
PITX1	ENST00000506438.5	TSL:1	c.-68-153G>T	intron	N/A	ENSP00000427542.1	P78337
PITX1	ENST00000507253.5	TSL:3	c.-68-153G>T	intron	N/A	ENSP00000422908.1	D6R9U1

Frequencies

GnomAD3 genomes

AF:

0.0522

AC:

7850

AN:

150334

Hom.:

331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.0698

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.000393

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0623

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.0703

Gnomad OTH

AF:

0.0630

GnomAD4 exome

AF:

0.0826

AC:

1267

AN:

15346

Hom.:

Cov.:

AF XY:

0.0822

AC XY:

694

AN XY:

8440

show subpopulations

African (AFR)

AF:

0.0145

AC:

AN:

344

American (AMR)

AF:

0.0625

AC:

AN:

512

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

AN:

436

East Asian (EAS)

AF:

0.00

AC:

AN:

550

South Asian (SAS)

AF:

0.0128

AC:

AN:

156

European-Finnish (FIN)

AF:

0.0800

AC:

142

AN:

1776

Middle Eastern (MID)

AF:

0.0375

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0863

AC:

908

AN:

10520

Other (OTH)

AF:

0.0854

AC:

AN:

972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0521

AC:

7843

AN:

150442

Hom.:

331

Cov.:

AF XY:

0.0519

AC XY:

3815

AN XY:

73502

show subpopulations

African (AFR)

AF:

0.0119

AC:

490

AN:

41264

American (AMR)

AF:

0.0697

AC:

1055

AN:

15136

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

572

AN:

3458

East Asian (EAS)

AF:

0.000394

AC:

AN:

5076

South Asian (SAS)

AF:

0.0131

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0623

AC:

628

AN:

10076

Middle Eastern (MID)

AF:

0.124

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0703

AC:

4733

AN:

67326

Other (OTH)

AF:

0.0623

AC:

130

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

376

751

1127

1502

1878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0560

Hom.:

Bravo

AF:

0.0520

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

-1.5

PromoterAI

0.010

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=300/0

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