rs8866

Variant names:

• chr17-67377863-C-A
• rs8866
• NM_012417.4:c.-292C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-67377863-C-A
• chr17-67377863-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012417.4(PITPNC1):​c.-292C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000474 in 211,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: PITPNC1 NM_012417.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 0 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]

ENSG00000297739 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNC1	NM_012417.4	c.-292C>A		5_prime_UTR_variant	Exon 1 of 9	ENST00000581322.6	NP_036549.2
PITPNC1	NM_181671.3	c.-292C>A		5_prime_UTR_variant	Exon 1 of 10		NP_858057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNC1	ENST00000581322.6	c.-292C>A		5_prime_UTR_variant	Exon 1 of 9	1	NM_012417.4	ENSP00000464006.1
PITPNC1	ENST00000580974.6	c.-292C>A		5_prime_UTR_variant	Exon 1 of 10	1		ENSP00000463626.1
ENSG00000297739	ENST00000750645.1	n.43G>T		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000474 AC: 1 AN: 211024 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 107276

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 5504

American (AMR) AF: 0.00 AC: 0 AN: 5462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7384

East Asian (EAS) AF: 0.00 AC: 0 AN: 17268

South Asian (SAS) AF: 0.00 AC: 0 AN: 6216

European-Finnish (FIN) AF: 0.0000545 AC: 1 AN: 18360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1094

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 135770

Other (OTH) AF: 0.00 AC: 0 AN: 13966

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.86
PhyloP100		-0.089
PromoterAI		-0.11	Neutral

Splicing

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

Other links and lift over

dbSNP: rs8866; hg19: chr17-65373979;