Variant chr1-119803126-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032044.4(REG4):c.107A>G(p.Tyr36Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

REG4
NM_032044.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.694

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3553432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REG4	NM_032044.4 linkuse as main transcript	c.107A>G	p.Tyr36Cys	missense_variant	3/6	ENST00000256585.10	NP_114433.1	Q9BYZ8-1
REG4	NM_001159352.2 linkuse as main transcript	c.107A>G	p.Tyr36Cys	missense_variant	4/7		NP_001152824.1	Q9BYZ8-1
REG4	NM_001159353.2 linkuse as main transcript	c.107A>G	p.Tyr36Cys	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.107A>G	p.Tyr36Cys	missense_variant	3/6	1	NM_032044.4	ENSP00000256585.5	Q9BYZ8-1
REG4	ENST00000354219.5 linkuse as main transcript	c.107A>G	p.Tyr36Cys	missense_variant	4/7	1		ENSP00000346158.1	Q9BYZ8-1
REG4	ENST00000369401.4 linkuse as main transcript	c.107A>G	p.Tyr36Cys	missense_variant	3/3	1		ENSP00000358409.4	Q9BYZ8-2
REG4	ENST00000530654.1 linkuse as main transcript	c.107A>G	p.Tyr36Cys	missense_variant	2/4	5		ENSP00000437135.1	E9PNV6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000536

AC:

AN:

186684

Hom.:

AF XY:

0.00

AC XY:

AN XY:

98610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000617

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1384242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680904

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000513

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 29, 2023

The c.107A>G (p.Y36C) 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 107, causing the tyrosine (Y) at amino acid position 36 to be replaced by a cysteine (C). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

T;T;T;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.81

.;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.36

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;M;.;M

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.4

D;D;D;D

REVEL

Benign

0.15

Sift

Benign

0.037

D;D;T;D

Sift4G

Benign

0.062

T;T;T;D

Polyphen

1.0

D;D;.;D

Vest4

0.61

MutPred

0.47

Loss of ubiquitination at K38 (P = 0.0593);Loss of ubiquitination at K38 (P = 0.0593);Loss of ubiquitination at K38 (P = 0.0593);Loss of ubiquitination at K38 (P = 0.0593);

MVP

0.36

MPC

0.49

ClinPred

0.98

GERP RS

5.1

Varity_R

0.22

gMVP

0.49

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