Variant rs9358856 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017640.6(CARMIL1):c.229G>A(p.Val77Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,610,102 control chromosomes in the GnomAD database, including 17,584 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.14 ( 1522 hom., cov: 31)

Exomes 𝑓: 0.15 ( 16062 hom. )

Consequence

CARMIL1
NM_017640.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.281

Variant links:

Genes affected

CARMIL1 (HGNC:21581): (capping protein regulator and myosin 1 linker 1) Involved in several processes, including actin filament network formation; plasma membrane bounded cell projection organization; and positive regulation of cellular component organization. Located in several cellular components, including lamellipodium; macropinosome; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

CARMIL1 links:

CMAHP (HGNC:2098): (cytidine monophospho-N-acetylneuraminic acid hydroxylase, pseudogene) Sialic acids are terminal components of the carbohydrate chains of glycoconjugates involved in ligand-receptor, cell-cell, and cell-pathogen interactions. The two most common forms of sialic acid found in mammalian cells are N-acetylneuraminic acid (Neu5Ac) and its hydroxylated derivative, N-glycolylneuraminic acid (Neu5Gc). Studies of sialic acid distribution show that Neu5Gc is not detectable in normal human tissues although it was an abundant sialic acid in other mammals. Neu5Gc is, in actuality, immunogenic in humans. The absense of Neu5Gc in humans is due to a deletion within the human gene CMAH encoding cytidine monophosphate-N-acetylneuraminic acid hydroxylase, an enzyme responsible for Neu5Gc biosynthesis. Sequences encoding the mouse, pig, and chimpanzee hydroxylase enzymes were obtained by cDNA cloning and found to be highly homologous. However, the homologous human cDNA differs from these cDNAs by a 92-bp deletion in the 5' region. This deletion, corresponding to exon 6 of the mouse hydroxylase gene, causes a frameshift mutation and premature termination of the polypeptide chain in human. It seems unlikely that the truncated human hydroxylase mRNA encodes for an active enzyme explaining why Neu5Gc is undetectable in normal human tissues. Human genomic DNA also shows evidence of this deletion which does not occur in the genomes of African great apes. Nonetheless, the CMAH gene maps to 6p21.32 in humans and great apes indicating that mutation of the CMAH gene occurred following human divergence from chimpanzees and bonobos. [provided by RefSeq, Jul 2008]

CMAHP links:

LOC124901281 (HGNC:):

LOC124901281 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004101813).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARMIL1	NM_017640.6 link	c.229G>A	p.Val77Ile	missense_variant	4/37	ENST00000329474.7	NP_060110.4	Q5VZK9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7 link	c.229G>A	p.Val77Ile	missense_variant	4/37	1	NM_017640.6	ENSP00000331983.6		Q5VZK9-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20642

AN:

151170

Hom.:

1522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0854

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.162

AC:

40231

AN:

248160

Hom.:

3525

AF XY:

0.163

AC XY:

21893

AN XY:

134664

show subpopulations

Gnomad AFR exome

AF:

0.0855

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.240

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.145

AC:

212028

AN:

1458814

Hom.:

16062

Cov.:

AF XY:

0.146

AC XY:

105941

AN XY:

725690

show subpopulations

Gnomad4 AFR exome

AF:

0.0844

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.220

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.183

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.150

GnomAD4 genome

AF:

0.136

AC:

20636

AN:

151288

Hom.:

1522

Cov.:

AF XY:

0.141

AC XY:

10431

AN XY:

73836

show subpopulations

Gnomad4 AFR

AF:

0.0853

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.224

Gnomad4 SAS

AF:

0.181

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.142

Hom.:

4167

Bravo

AF:

0.132

TwinsUK

AF:

0.132

AC:

489

ALSPAC

AF:

0.130

AC:

500

ESP6500AA

AF:

0.0770

AC:

299

ESP6500EA

AF:

0.144

AC:

1196

ExAC

AF:

0.160

AC:

19328

Asia WGS

AF:

0.178

AC:

622

AN:

3476

EpiCase

AF:

0.142

EpiControl

AF:

0.138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.011

DANN

Benign

0.83

DEOGEN2

Benign

0.018

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.020

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.62

REVEL

Benign

0.018

Sift

Benign

0.23

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.013

MPC

0.25

ClinPred

0.0011

GERP RS

-1.4

Varity_R

0.026

gMVP

0.077

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