Genetic Variant NM_032044.4: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

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NM_032044.4:c.*456G>A

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