Variant chr1-119798502-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.404A>G(p.Asn135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,808 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. N135H) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

REG4
NM_032044.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.09

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=0.0435459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REG4	NM_032044.4 linkuse as main transcript	c.404A>G	p.Asn135Ser	missense_variant	5/6	ENST00000256585.10	NP_114433.1	Q9BYZ8-1
REG4	NM_001159352.2 linkuse as main transcript	c.404A>G	p.Asn135Ser	missense_variant	6/7		NP_001152824.1	Q9BYZ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
REG4	ENST00000256585.10 linkuse as main transcript	c.404A>G	p.Asn135Ser	missense_variant	5/6	1	NM_032044.4	ENSP00000256585.5	Q9BYZ8-1
REG4	ENST00000354219.5 linkuse as main transcript	c.404A>G	p.Asn135Ser	missense_variant	6/7	1		ENSP00000346158.1	Q9BYZ8-1
REG4	ENST00000530654.1 linkuse as main transcript	c.303+1223A>G		intron_variant		5		ENSP00000437135.1	E9PNV6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251368

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460808

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

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

Jan 31, 2023

The c.404A>G (p.N135S) alteration is located in exon 6 (coding exon 4) of the REG4 gene. This alteration results from a A to G substitution at nucleotide position 404, causing the asparagine (N) at amino acid position 135 to be replaced by a serine (S). 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

0.066

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.011

DANN

Benign

0.39

DEOGEN2

Benign

0.0015

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.33

.;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.42

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.60

N;N

REVEL

Benign

0.0060

Sift

Benign

0.75

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.0

B;B

Vest4

0.12

MutPred

0.36

Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);

MVP

0.061

MPC

0.074

ClinPred

0.030

GERP RS

-7.9

Varity_R

0.028

gMVP

0.036

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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