rs11959298

Positions:

• chr5-135031850-A-G

Variant summary

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

The NM_002653.5(PITX1):​c.170-342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 386,436 control chromosomes in the GnomAD database, including 10,269 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 0.24 (7589 hom., cov: 33)
  • Exomes 𝑓: 0.12 (2680 hom.)
• Consequence: PITX1 NM_002653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITX1	NM_002653.5	c.170-342T>C		intron_variant		ENST00000265340.12	NP_002644.4
PITX1	XM_047417318.1	c.272-342T>C		intron_variant			XP_047273274.1
PITX1	XM_047417319.1	c.-176-342T>C		intron_variant			XP_047273275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12	c.170-342T>C		intron_variant		1	NM_002653.5	ENSP00000265340.6

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36402 AN: 151932 Hom.: 7547 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0673

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0512

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.119 AC: 27998 AN: 234386 Hom.: 2680 Cov.: 0 AF XY: 0.114 AC XY: 13821 AN XY: 121232

Gnomad4 AFR exome AF: 0.555

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.0709

Gnomad4 EAS exome AF: 0.000139

Gnomad4 SAS exome AF: 0.0551

Gnomad4 FIN exome AF: 0.0814

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.240 AC: 36527 AN: 152050 Hom.: 7589 Cov.: 33 AF XY: 0.232 AC XY: 17214 AN XY: 74348

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.0673

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.217

Alfa AF: 0.176 Hom.: 1141

Bravo AF: 0.267

Asia WGS AF: 0.0640 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.65

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: rs11959298; hg19: chr5-134367540;