16-8856890-C-T

Variant names:

• chr16-8856890-C-T
• rs1657070
• NM_014316.4:c.281+1460G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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: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]

PMM2 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation type I

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• PMM2-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, ClinGen

LOC100130283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CARHSP1	NM_014316.4	c.281+1460G>A		intron_variant	Intron 3 of 3	ENST00000311052.10	NP_055131.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARHSP1	ENST00000311052.10	c.281+1460G>A		intron_variant	Intron 3 of 3	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

African (AFR) AF: 0.436 AC: 18033 AN: 41400

American (AMR) AF: 0.721 AC: 11007 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2460 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3723 AN: 5162

South Asian (SAS) AF: 0.736 AC: 3542 AN: 4814

European-Finnish (FIN) AF: 0.707 AC: 7477 AN: 10574

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47510 AN: 67908

Other (OTH) AF: 0.652 AC: 1378 AN: 2114

Alfa AF: 0.665 Hom.: 11678

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
PhyloP100		-0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs1657070; hg19: chr16-8950747;