Genetic Variant REG4:c.*456G>A (chr1-119794162-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032044.4(REG4):c.*456G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 534,118 control chromosomes in the GnomAD database, including 82,448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 26568 hom., cov: 30)

Exomes 𝑓: 0.53 ( 55880 hom. )

Consequence

REG4
NM_032044.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.443

Publications

19 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REG4	NM_032044.4 link	c.*456G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000256585.10	NP_114433.1	Q9BYZ8-1
REG4	NM_001159352.2 link	c.*456G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001152824.1	Q9BYZ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REG4	ENST00000256585.10 link	c.*456G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_032044.4	ENSP00000256585.5		Q9BYZ8-1
REG4	ENST00000354219.5 link	c.*456G>A		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000346158.1		Q9BYZ8-1

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87886

AN:

151674

Hom.:

26532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.736

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.573

GnomAD2 exomes

AF:

0.513

AC:

125090

AN:

243924

AF XY:

0.522

show subpopulations

Gnomad AFR exome

AF:

0.741

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.567

Gnomad EAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.540

GnomAD4 exome

AF:

0.531

AC:

202962

AN:

382326

Hom.:

55880

Cov.:

AF XY:

0.539

AC XY:

117300

AN XY:

217722

show subpopulations

African (AFR)

AF:

0.742

AC:

7843

AN:

10568

American (AMR)

AF:

0.353

AC:

12813

AN:

36336

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

6713

AN:

11792

East Asian (EAS)

AF:

0.230

AC:

3049

AN:

13228

South Asian (SAS)

AF:

0.584

AC:

38994

AN:

66764

European-Finnish (FIN)

AF:

0.484

AC:

15135

AN:

31270

Middle Eastern (MID)

AF:

0.630

AC:

1803

AN:

2864

European-Non Finnish (NFE)

AF:

0.557

AC:

107378

AN:

192730

Other (OTH)

AF:

0.550

AC:

9234

AN:

16774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

5373

10746

16119

21492

26865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.580

AC:

87973

AN:

151792

Hom.:

26568

Cov.:

AF XY:

0.570

AC XY:

42288

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.736

AC:

30450

AN:

41354

American (AMR)

AF:

0.445

AC:

6783

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2014

AN:

3466

East Asian (EAS)

AF:

0.235

AC:

1212

AN:

5160

South Asian (SAS)

AF:

0.569

AC:

2733

AN:

4800

European-Finnish (FIN)

AF:

0.477

AC:

5015

AN:

10506

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.559

AC:

37946

AN:

67938

Other (OTH)

AF:

0.575

AC:

1212

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1783

3567

5350

7134

8917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.567

Hom.:

84441

Bravo

AF:

0.580

Asia WGS

AF:

0.502

AC:

1748

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

(source)

DANN

Benign

0.59

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr1-119794162-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over