16-8856890-C-T

Position:

• chr16-8856890-C-T

Variant summary

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

The NM_014316.4(CARHSP1):​c.281+1460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,910 control chromosomes in the GnomAD database, including 31,378 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 0.63 (31378 hom., cov: 31)
• Consequence: CARHSP1 NM_014316.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811

Genes affected

CARHSP1 (HGNC:17150): (calcium regulated heat stable protein 1) Enables mRNA 3'-UTR binding activity. Predicted to be involved in regulation of mRNA stability. Predicted to be located in P granule and cytosol. Predicted to be active in cytoplasm. Predicted to colocalize with cytoplasmic exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

PMM2 (HGNC:):

PMM2 (HGNC:9115): (phosphomannomutase 2) The protein encoded by this gene catalyzes the isomerization of mannose 6-phosphate to mannose 1-phosphate, which is a precursor to GDP-mannose necessary for the synthesis of dolichol-P-oligosaccharides. Mutations in this gene have been shown to cause defects in glycoprotein biosynthesis, which manifests as carbohydrate-deficient glycoprotein syndrome type I. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARHSP1	NM_014316.4	c.281+1460G>A		intron_variant		ENST00000311052.10	NP_055131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARHSP1	ENST00000311052.10	c.281+1460G>A		intron_variant		1	NM_014316.4	ENSP00000311847.4

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95777 AN: 151792 Hom.: 31365 Cov.: 31

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.631 AC: 95822 AN: 151910 Hom.: 31378 Cov.: 31 AF XY: 0.635 AC XY: 47091 AN XY: 74216

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.652

Alfa AF: 0.669 Hom.: 6869

Bravo AF: 0.624

Asia WGS AF: 0.701 AC: 2438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.47
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs1657070; hg19: chr16-8950747;