Genetic Variant CARHSP1:p.Arg35Arg (chr16-8859224-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014316.4(CARHSP1):c.105G>C(p.Arg35Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,597,628 control chromosomes in the GnomAD database, including 325,851 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 0.56 ( 22972 hom., cov: 23)

Exomes 𝑓: 0.64 ( 302879 hom. )

Consequence

CARHSP1
NM_014316.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.162

Variant links:

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]

CARHSP1 links:

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 links:

LOC100130283 (HGNC:):

LOC100130283 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.8201111E-6).

BP7

Synonymous conserved (PhyloP=-0.162 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARHSP1	NM_014316.4 link	c.105G>C	p.Arg35Arg	synonymous_variant	Exon 2 of 4	ENST00000311052.10	NP_055131.2	Q9Y2V2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARHSP1	ENST00000311052.10 link	c.105G>C	p.Arg35Arg	synonymous_variant	Exon 2 of 4	1	NM_014316.4	ENSP00000311847.4		Q9Y2V2

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

78081

AN:

139552

Hom.:

22971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.372

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.653

Gnomad EAS

AF:

0.664

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.571

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.569

GnomAD3 exomes

AF:

0.621

AC:

151805

AN:

244478

Hom.:

47882

AF XY:

0.632

AC XY:

83970

AN XY:

132908

show subpopulations

Gnomad AFR exome

AF:

0.371

Gnomad AMR exome

AF:

0.528

Gnomad ASJ exome

AF:

0.645

Gnomad EAS exome

AF:

0.680

Gnomad SAS exome

AF:

0.691

Gnomad FIN exome

AF:

0.672

Gnomad NFE exome

AF:

0.645

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.642

AC:

935909

AN:

1457958

Hom.:

302879

Cov.:

AF XY:

0.644

AC XY:

466947

AN XY:

725266

show subpopulations

Gnomad4 AFR exome

AF:

0.362

Gnomad4 AMR exome

AF:

0.524

Gnomad4 ASJ exome

AF:

0.651

Gnomad4 EAS exome

AF:

0.683

Gnomad4 SAS exome

AF:

0.693

Gnomad4 FIN exome

AF:

0.667

Gnomad4 NFE exome

AF:

0.649

Gnomad4 OTH exome

AF:

0.630

GnomAD4 genome

AF:

0.559

AC:

78109

AN:

139670

Hom.:

22972

Cov.:

AF XY:

0.559

AC XY:

37259

AN XY:

66682

show subpopulations

Gnomad4 AFR

AF:

0.371

Gnomad4 AMR

AF:

0.511

Gnomad4 ASJ

AF:

0.653

Gnomad4 EAS

AF:

0.664

Gnomad4 SAS

AF:

0.696

Gnomad4 FIN

AF:

0.667

Gnomad4 NFE

AF:

0.644

Gnomad4 OTH

AF:

0.566

Alfa

AF:

0.547

Hom.:

3172

Bravo

AF:

0.543

TwinsUK

AF:

0.650

AC:

2409

ALSPAC

AF:

0.657

AC:

2531

ESP6500AA

AF:

0.387

AC:

1699

ESP6500EA

AF:

0.641

AC:

5509

ExAC

AF:

0.618

AC:

74921

Asia WGS

AF:

0.643

AC:

2237

AN:

3478

EpiCase

AF:

0.648

EpiControl

AF:

0.647

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

3.4

DANN

Benign

0.95

FATHMM_MKL

Uncertain

0.87

MetaRNN

Benign

0.0000028

PROVEAN

Pathogenic

-6.0

GERP RS

0.015

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over