Variant chr1-119808750-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032044.4(REG4):c.20G>A(p.Arg7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,650 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7W) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

REG4
NM_032044.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15810567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REG4	NM_032044.4 linkuse as main transcript	c.20G>A	p.Arg7Gln	missense_variant	2/6	ENST00000256585.10	NP_114433.1	Q9BYZ8-1
REG4	NM_001159352.2 linkuse as main transcript	c.20G>A	p.Arg7Gln	missense_variant	3/7		NP_001152824.1	Q9BYZ8-1
REG4	NM_001159353.2 linkuse as main transcript	c.20G>A	p.Arg7Gln	missense_variant	2/3		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.20G>A	p.Arg7Gln	missense_variant	2/6	1	NM_032044.4	ENSP00000256585.5	Q9BYZ8-1
REG4	ENST00000354219.5 linkuse as main transcript	c.20G>A	p.Arg7Gln	missense_variant	3/7	1		ENSP00000346158.1	Q9BYZ8-1
REG4	ENST00000369401.4 linkuse as main transcript	c.20G>A	p.Arg7Gln	missense_variant	2/3	1		ENSP00000358409.4	Q9BYZ8-2
REG4	ENST00000530654.1 linkuse as main transcript	c.20G>A	p.Arg7Gln	missense_variant	1/4	5		ENSP00000437135.1	E9PNV6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251246

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461650

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

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

Jun 07, 2024

The c.20G>A (p.R7Q) alteration is located in exon 3 (coding exon 1) of the REG4 gene. This alteration results from a G to A substitution at nucleotide position 20, causing the arginine (R) at amino acid position 7 to be replaced by a glutamine (Q). 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

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.0083

T;T;T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.54

.;T;T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;L;.;L

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.46

N;N;N;N

REVEL

Benign

0.028

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.0070

B;B;.;D

Vest4

0.17

MutPred

0.48

Loss of MoRF binding (P = 0.001);Loss of MoRF binding (P = 0.001);Loss of MoRF binding (P = 0.001);Loss of MoRF binding (P = 0.001);

MVP

0.15

MPC

0.11

ClinPred

0.049

GERP RS

2.9

Varity_R

0.028

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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