rs4237

Variant names:

• chr1-23787639-G-A
• rs4237
• NM_020362.5:c.*263G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PITHD1	NM_020362.5	c.*263G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000246151.9	NP_065095.2
PITHD1	XM_011541804.2	c.*263G>A		3_prime_UTR_variant	Exon 5 of 5		XP_011540106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITHD1	ENST00000246151.9	c.*263G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_020362.5	ENSP00000246151.4
PITHD1	ENST00000374524.1	c.*263G>A		3_prime_UTR_variant	Exon 4 of 4	3		ENSP00000363648.1

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

African (AFR) AF: 0.781 AC: 3155 AN: 4040

American (AMR) AF: 0.660 AC: 2264 AN: 3432

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 2647 AN: 4642

East Asian (EAS) AF: 0.636 AC: 6072 AN: 9554

South Asian (SAS) AF: 0.739 AC: 2805 AN: 3798

European-Finnish (FIN) AF: 0.577 AC: 4919 AN: 8530

Middle Eastern (MID) AF: 0.733 AC: 437 AN: 596

European-Non Finnish (NFE) AF: 0.587 AC: 44282 AN: 75450

Other (OTH) AF: 0.623 AC: 5047 AN: 8104

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

African (AFR) AF: 0.775 AC: 32136 AN: 41454

American (AMR) AF: 0.633 AC: 9684 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3470

East Asian (EAS) AF: 0.569 AC: 2939 AN: 5168

South Asian (SAS) AF: 0.721 AC: 3472 AN: 4818

European-Finnish (FIN) AF: 0.563 AC: 5953 AN: 10572

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39257 AN: 67978

Other (OTH) AF: 0.622 AC: 1313 AN: 2110

Alfa AF: 0.598 Hom.: 32849

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
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4237; hg19: chr1-24114129;