dbSNP rs111225899: 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:

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=-0.41).

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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rs111225899

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