rs2994809

Variant names:

• chr1-119809354-T-C
• rs2994809
• NM_032044.4:c.-94-491A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
REG4	NM_032044.4	c.-94-491A>G		intron_variant	Intron 1 of 5	ENST00000256585.10	NP_114433.1
REG4	NM_001159352.2	c.-268-152A>G		intron_variant	Intron 1 of 6		NP_001152824.1
REG4	NM_001159353.2	c.-94-491A>G		intron_variant	Intron 1 of 2		NP_001152825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REG4	ENST00000256585.10	c.-94-491A>G		intron_variant	Intron 1 of 5	1	NM_032044.4	ENSP00000256585.5
REG4	ENST00000354219.5	c.-268-152A>G		intron_variant	Intron 1 of 6	1		ENSP00000346158.1
REG4	ENST00000369401.4	c.-94-491A>G		intron_variant	Intron 1 of 2	1		ENSP00000358409.4

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

African (AFR) AF: 0.967 AC: 40164 AN: 41532

American (AMR) AF: 0.892 AC: 13642 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3342 AN: 3470

East Asian (EAS) AF: 0.501 AC: 2584 AN: 5154

South Asian (SAS) AF: 0.902 AC: 4344 AN: 4816

European-Finnish (FIN) AF: 0.873 AC: 9249 AN: 10598

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.903 AC: 61402 AN: 67990

Other (OTH) AF: 0.908 AC: 1919 AN: 2114

Alfa AF: 0.910 Hom.: 106670

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
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2994809; hg19: chr1-120351977;