rs2994809

Positions:

• chr1-119809354-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032044.4(REG4):​c.-94-491A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,176 control chromosomes in the GnomAD database, including 62,943 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 0.91 (62943 hom., cov: 33)
• Consequence: REG4 NM_032044.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REG4	NM_032044.4	c.-94-491A>G		intron_variant		ENST00000256585.10
REG4	NM_001159352.2	c.-268-152A>G		intron_variant
REG4	NM_001159353.2	c.-94-491A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REG4	ENST00000256585.10	c.-94-491A>G		intron_variant		1	NM_032044.4	P1
REG4	ENST00000354219.5	c.-268-152A>G		intron_variant		1		P1
REG4	ENST00000369401.4	c.-94-491A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137691 AN: 152058 Hom.: 62891 Cov.: 33

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.903

Gnomad OTH AF: 0.912

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.906 AC: 137798 AN: 152176 Hom.: 62943 Cov.: 33 AF XY: 0.903 AC XY: 67163 AN XY: 74406

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.892

Gnomad4 ASJ AF: 0.963

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.903

Gnomad4 OTH AF: 0.908

Alfa AF: 0.910 Hom.: 84840

Bravo AF: 0.907

Asia WGS AF: 0.727 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs2994809; hg19: chr1-120351977;