5-135034150-CCCGGCT-C

Position:

• chr5-135034150-CCCGGCT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002653.5(PITX1):​c.-275_-270del 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.777

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)

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
PITX1	NM_002653.5	c.-275_-270del		5_prime_UTR_variant	1/3	ENST00000265340.12
PITX1-AS1	NR_161235.1	n.267+630_267+635del		intron_variant, non_coding_transcript_variant
PITX1	XM_047417318.1	c.35-207_35-202del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITX1	ENST00000265340.12	c.-275_-270del		5_prime_UTR_variant	1/3	1	NM_002653.5	P1
PITX1-AS1	ENST00000624272.3	n.261+630_261+635del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 67316 AN: 149236 Hom.: 17180 Cov.: 0

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.: 53 AF XY: 0.150 AC XY: 155 AN XY: 1030

Gnomad4 AFR exome AF: 0.692

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.0909

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.452 AC: 67447 AN: 149342 Hom.: 17243 Cov.: 0 AF XY: 0.449 AC XY: 32681 AN XY: 72866

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.426

Bravo AF: 0.478

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 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs372983845; hg19: chr5-134369840;