Genetic Variant NM_002653.5:c.-275_-270delAGCCGG (chr5-135034150-CCCGGCT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002653.5(PITX1):c.-275_-270delAGCCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,098 control chromosomes in the GnomAD database, including 17,296 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.45 ( 17243 hom., cov: 0)

Exomes 𝑓: 0.16 ( 53 hom. )

Consequence

PITX1
NM_002653.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.777

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 -10 ACMG points.

BP6

Variant 5-135034150-CCCGGCT-C is Benign according to our data. Variant chr5-135034150-CCCGGCT-C is described in ClinVar as [Benign]. Clinvar id is 1268490.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5 link	c.-275_-270delAGCCGG	5_prime_UTR_variant	Exon 1 of 3	ENST00000265340.12	NP_002644.4	P78337X5D9A5
PITX1-AS1	NR_161235.1 link	n.267+630_267+635delCGGCTC	intron_variant	Intron 1 of 5
PITX1	XM_047417318.1 link	c.35-207_35-202delAGCCGG	intron_variant	Intron 1 of 3		XP_047273274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12 link	c.-275_-270delAGCCGG		5_prime_UTR_variant	Exon 1 of 3	1	NM_002653.5	ENSP00000265340.6		P78337

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

67316

AN:

149236

Hom.:

17180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.461

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.422

GnomAD4 exome

AF:

0.161

AC:

282

AN:

1756

Hom.:

AF XY:

0.150

AC XY:

155

AN XY:

1030

show subpopulations

African (AFR)

AF:

0.692

AC:

AN:

American (AMR)

AF:

0.310

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

AN:

East Asian (EAS)

AF:

0.404

AC:

AN:

South Asian (SAS)

AF:

0.0909

AC:

AN:

European-Finnish (FIN)

AF:

0.156

AC:

AN:

212

Middle Eastern (MID)

AF:

0.100

AC:

AN:

European-Non Finnish (NFE)

AF:

0.133

AC:

163

AN:

1228

Other (OTH)

AF:

0.234

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.452

AC:

67447

AN:

149342

Hom.:

17243

Cov.:

AF XY:

0.449

AC XY:

32681

AN XY:

72866

show subpopulations

African (AFR)

AF:

0.692

AC:

28150

AN:

40674

American (AMR)

AF:

0.486

AC:

7340

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1001

AN:

3444

East Asian (EAS)

AF:

0.461

AC:

2250

AN:

4884

South Asian (SAS)

AF:

0.445

AC:

2117

AN:

4760

European-Finnish (FIN)

AF:

0.297

AC:

3031

AN:

10208

Middle Eastern (MID)

AF:

0.273

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.332

AC:

22249

AN:

66984

Other (OTH)

AF:

0.426

AC:

886

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1578

3156

4734

6312

7890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.156

Hom.:

272

Bravo

AF:

0.478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 14, 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

PhyloP100

0.78

Mutation Taster

=297/3

polymorphism (auto)

(source)

Splicing

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

Publications

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NM_002653.5:c.-275_-270delAGCCGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over