rs4237

Positions:

• chr1-23787639-G-A

Variant summary

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

The NM_020362.5(PITHD1):​c.*263G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 270,208 control chromosomes in the GnomAD database, including 53,637 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 0.64 (31701 hom., cov: 32)
  • Exomes 𝑓: 0.61 (21936 hom.)
• Consequence: PITHD1 NM_020362.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

Genes affected

PITHD1 (HGNC:25022): (PITH domain containing 1) Involved in positive regulation of megakaryocyte differentiation and positive regulation of transcription, DNA-templated. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITHD1	NM_020362.5	c.*263G>A		3_prime_UTR_variant	6/6	ENST00000246151.9	NP_065095.2
PITHD1	XM_011541804.2	c.*263G>A		3_prime_UTR_variant	5/5		XP_011540106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITHD1	ENST00000246151.9	c.*263G>A		3_prime_UTR_variant	6/6	1	NM_020362.5	ENSP00000246151	P1
PITHD1	ENST00000374524.1	c.*263G>A		3_prime_UTR_variant	4/4	3		ENSP00000363648

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97339 AN: 151944 Hom.: 31670 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.627

GnomAD4 exome AF: 0.606 AC: 71628 AN: 118146 Hom.: 21936 Cov.: 0 AF XY: 0.606 AC XY: 36534 AN XY: 60240

Gnomad4 AFR exome AF: 0.781

Gnomad4 AMR exome AF: 0.660

Gnomad4 ASJ exome AF: 0.570

Gnomad4 EAS exome AF: 0.636

Gnomad4 SAS exome AF: 0.739

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.623

GnomAD4 genome AF: 0.641 AC: 97424 AN: 152062 Hom.: 31701 Cov.: 32 AF XY: 0.644 AC XY: 47892 AN XY: 74316

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.622

Alfa AF: 0.596 Hom.: 26949

Bravo AF: 0.652

Asia WGS AF: 0.651 AC: 2263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.75

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: rs4237; hg19: chr1-24114129;