Variant 1-119803157-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032044.4(REG4):c.76A>G(p.Met26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,519,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

REG4
NM_032044.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.183

Variant links:

Genes affected

REG4 (HGNC:22977): (regenerating family member 4) Enables heparin binding activity and mannan binding activity. Predicted to act upstream of or within response to bacterium. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

REG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047395498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REG4	NM_032044.4 linkuse as main transcript	c.76A>G	p.Met26Val	missense_variant	3/6	ENST00000256585.10	NP_114433.1	Q9BYZ8-1
REG4	NM_001159352.2 linkuse as main transcript	c.76A>G	p.Met26Val	missense_variant	4/7		NP_001152824.1	Q9BYZ8-1
REG4	NM_001159353.2 linkuse as main transcript	c.76A>G	p.Met26Val	missense_variant	3/3		NP_001152825.1	Q9BYZ8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
REG4	ENST00000256585.10 linkuse as main transcript	c.76A>G	p.Met26Val	missense_variant	3/6	1	NM_032044.4	ENSP00000256585.5	Q9BYZ8-1
REG4	ENST00000354219.5 linkuse as main transcript	c.76A>G	p.Met26Val	missense_variant	4/7	1		ENSP00000346158.1	Q9BYZ8-1
REG4	ENST00000369401.4 linkuse as main transcript	c.76A>G	p.Met26Val	missense_variant	3/3	1		ENSP00000358409.4	Q9BYZ8-2
REG4	ENST00000530654.1 linkuse as main transcript	c.76A>G	p.Met26Val	missense_variant	2/4	5		ENSP00000437135.1	E9PNV6

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000171

AC:

AN:

175860

Hom.:

AF XY:

0.00

AC XY:

AN XY:

92512

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000249

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1367002

Hom.:

Cov.:

AF XY:

0.0000119

AC XY:

AN XY:

670112

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.0000346

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000562

Gnomad4 OTH exome

AF:

0.0000533

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000645

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000842

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.76A>G (p.M26V) alteration is located in exon 4 (coding exon 2) of the REG4 gene. This alteration results from a A to G substitution at nucleotide position 76, causing the methionine (M) at amino acid position 26 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.63

CADD

Benign

2.0

DANN

Benign

0.29

DEOGEN2

Benign

0.0075

T;T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.55

.;T;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.047

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.76

N;N;.;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.70

N;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.72

T;T;T;T

Sift4G

Benign

0.83

T;T;T;T

Polyphen

0.0010

B;B;.;B

Vest4

0.20

MVP

0.048

MPC

0.096

ClinPred

0.027

GERP RS

-4.6

Varity_R

0.079

gMVP

0.20

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over