17-67502704-T-C

Variant names:

• chr17-67502704-T-C
• rs2949942
• NM_012417.4:c.49-30098T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012417.4(PITPNC1):​c.49-30098T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,810 control chromosomes in the GnomAD database, including 41,372 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 0.74 (41372 hom., cov: 31)
• Consequence: PITPNC1 NM_012417.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 8 publications found

Genes affected

PITPNC1 (HGNC:21045): (phosphatidylinositol transfer protein cytoplasmic 1) This gene encodes a member of the phosphatidylinositol transfer protein family. The encoded cytoplasmic protein plays a role in multiple processes including cell signaling and lipid metabolism by facilitating the transfer of phosphatidylinositol between membrane compartments. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 1. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNC1	NM_012417.4	c.49-30098T>C		intron_variant	Intron 1 of 8	ENST00000581322.6	NP_036549.2
PITPNC1	NM_181671.3	c.49-30098T>C		intron_variant	Intron 1 of 9		NP_858057.1
PITPNC1	XM_047435746.1	c.-21-30098T>C		intron_variant	Intron 1 of 8		XP_047291702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNC1	ENST00000581322.6	c.49-30098T>C		intron_variant	Intron 1 of 8	1	NM_012417.4	ENSP00000464006.1
PITPNC1	ENST00000580974.6	c.49-30098T>C		intron_variant	Intron 1 of 9	1		ENSP00000463626.1
PITPNC1	ENST00000584554.1	c.-21-30098T>C		intron_variant	Intron 2 of 5	5		ENSP00000464364.1
PITPNC1	ENST00000584471.5	c.-21-30098T>C		intron_variant	Intron 1 of 4	5		ENSP00000464584.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111792 AN: 151688 Hom.: 41336 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.747

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.737 AC: 111883 AN: 151810 Hom.: 41372 Cov.: 31 AF XY: 0.737 AC XY: 54693 AN XY: 74198

African (AFR) AF: 0.675 AC: 27868 AN: 41284

American (AMR) AF: 0.744 AC: 11363 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2900 AN: 3468

East Asian (EAS) AF: 0.755 AC: 3895 AN: 5158

South Asian (SAS) AF: 0.788 AC: 3787 AN: 4806

European-Finnish (FIN) AF: 0.768 AC: 8105 AN: 10550

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51474 AN: 67970

Other (OTH) AF: 0.748 AC: 1576 AN: 2106

Alfa AF: 0.748 Hom.: 24782

Bravo AF: 0.732

Asia WGS AF: 0.723 AC: 2470 AN: 3414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.48
PhyloP100		-1.7
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: rs2949942; hg19: chr17-65498820;