rs6596189

Positions:

• chr5-135032479-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002653.5(PITX1):​c.170-971G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,108 control chromosomes in the GnomAD database, including 4,598 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 (4598 hom., cov: 33)
• Consequence: PITX1 NM_002653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITX1	NM_002653.5	c.170-971G>A		intron_variant		ENST00000265340.12
PITX1	XM_047417318.1	c.272-971G>A		intron_variant
PITX1	XM_047417319.1	c.-177+959G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITX1	ENST00000265340.12	c.170-971G>A		intron_variant		1	NM_002653.5	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30223 AN: 151990 Hom.: 4563 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0670

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30331 AN: 152108 Hom.: 4598 Cov.: 33 AF XY: 0.192 AC XY: 14296 AN XY: 74376

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.0670

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0514

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.189

Alfa AF: 0.125 Hom.: 2399

Bravo AF: 0.221

Asia WGS AF: 0.0520 AC: 181 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.90

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

LitVar

Other links and lift over

dbSNP: rs6596189; hg19: chr5-134368169;