5-135034491-C-T

Position:

• chr5-135034491-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00600

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-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PITX1-AS1	NR_161235.1	n.267+951C>T		intron_variant, non_coding_transcript_variant
PITX1	XM_047417318.1	c.34+11G>A		intron_variant			XP_047273274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITX1-AS1	ENST00000624272.3	n.261+951C>T		intron_variant, non_coding_transcript_variant		2
	ENST00000620001.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30084 AN: 151678 Hom.: 4539 Cov.: 32

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: 22 AN: 416 Hom.: 3 Cov.: 0 AF XY: 0.0773 AC XY: 17 AN XY: 220

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0422

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0694

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.199 AC: 30186 AN: 151784 Hom.: 4572 Cov.: 32 AF XY: 0.192 AC XY: 14229 AN XY: 74216

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.0672

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.0503

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.188

Alfa AF: 0.168 Hom.: 441

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111225899; hg19: chr5-134370181;