Genetic Variant PITX1:c.-69+78G>A (chr5-135034491-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The ENST00000506438.5(PITX1):c.-69+78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,200 control chromosomes in the GnomAD database, including 4,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 4572 hom., cov: 32)

Exomes 𝑓: 0.053 ( 3 hom. )

Consequence

PITX1
ENST00000506438.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00600

Publications

1 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:

ENSG00000277619 (HGNC:):

ENSG00000277619 links:

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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=-0.41).

BP6

Variant 5-135034491-C-T is Benign according to our data. Variant chr5-135034491-C-T is described in ClinVar as [Benign]. Clinvar id is 1275056.Status of the report is criteria_provided_single_submitter, 1 stars.

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 rank	MANE	Protein	UniProt
PITX1-AS1	NR_161235.1 link	n.267+951C>T		intron_variant	Intron 1 of 5
PITX1	XM_047417318.1 link	c.34+11G>A		intron_variant	Intron 1 of 3		XP_047273274.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
PITX1	ENST00000506438.5 link	c.-69+78G>A	intron_variant	Intron 1 of 3	1	ENSP00000427542.1	P78337
PITX1	ENST00000507253.5 link	c.-69+196G>A	intron_variant	Intron 1 of 2	3	ENSP00000422908.1	D6R9U1
PITX1	ENST00000502676.1 link	c.-69+11G>A	intron_variant	Intron 1 of 2	3	ENSP00000423624.1	D6R955

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30084

AN:

151678

Hom.:

4539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.0672

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0492

Gnomad FIN

AF:

0.0754

Gnomad MID

AF:

0.0801

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.190

GnomAD4 exome

AF:

0.0529

AC:

AN:

416

Hom.:

Cov.:

AF XY:

0.0773

AC XY:

AN XY:

220

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0422

AC:

AN:

332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0694

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.199

AC:

30186

AN:

151784

Hom.:

4572

Cov.:

AF XY:

0.192

AC XY:

14229

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.423

AC:

17465

AN:

41312

American (AMR)

AF:

0.207

AC:

3156

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0672

AC:

233

AN:

3466

East Asian (EAS)

AF:

0.00175

AC:

AN:

5152

South Asian (SAS)

AF:

0.0503

AC:

242

AN:

4812

European-Finnish (FIN)

AF:

0.0754

AC:

799

AN:

10600

Middle Eastern (MID)

AF:

0.0828

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.116

AC:

7840

AN:

67862

Other (OTH)

AF:

0.188

AC:

397

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1048

2096

3143

4191

5239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.272

Hom.:

1702

Bravo

AF:

0.221

Asia WGS

AF:

0.0520

AC:

181

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 22, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

0.0060

PromoterAI

0.0088

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr5-135034491-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over