rs6872664

Positions:

• chr5-135031908-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.170-400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 229,816 control chromosomes in the GnomAD database, including 5,215 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 (4603 hom., cov: 33)
  • Exomes 𝑓: 0.10 (612 hom.)
• Consequence: PITX1 NM_002653.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

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=-0.91).
• 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.170-400G>A		intron_variant		ENST00000265340.12
PITX1	XM_047417318.1	c.272-400G>A		intron_variant
PITX1	XM_047417319.1	c.-176-400G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITX1	ENST00000265340.12	c.170-400G>A		intron_variant		1	NM_002653.5	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30225 AN: 152060 Hom.: 4568 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.100 AC: 7775 AN: 77638 Hom.: 612 Cov.: 0 AF XY: 0.0964 AC XY: 3859 AN XY: 40012

Gnomad4 AFR exome AF: 0.369

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.0671

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0435

Gnomad4 FIN exome AF: 0.0766

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.199 AC: 30333 AN: 152178 Hom.: 4603 Cov.: 33 AF XY: 0.192 AC XY: 14295 AN XY: 74414

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.189

Alfa AF: 0.162 Hom.: 385

Bravo AF: 0.221

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.53

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: rs6872664; hg19: chr5-134367598;