rs749573650

Variant names:

• chr8-22138498-C-G
• rs749573650
• NM_025232.4:c.763G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-22138498-C-G
• chr8-22138498-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025232.4(REEP4):​c.763G>C​(p.Val255Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V255M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: REEP4 NM_025232.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 1 publications found

Genes affected

REEP4 (HGNC:26176): (receptor accessory protein 4) Predicted to enable microtubule binding activity. Involved in mitotic nuclear membrane reassembly. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022554666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP4	NM_025232.4	c.763G>C	p.Val255Leu	missense_variant	Exon 8 of 8	ENST00000306306.8	NP_079508.2
REEP4	NM_001316964.2	c.608G>C	p.Arg203Pro	missense_variant	Exon 7 of 7		NP_001303893.1
REEP4	NM_001316965.2	c.*105G>C		3_prime_UTR_variant	Exon 7 of 7		NP_001303894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP4	ENST00000306306.8	c.763G>C	p.Val255Leu	missense_variant	Exon 8 of 8	1	NM_025232.4	ENSP00000303482.3
REEP4	ENST00000334530.9	c.*105G>C		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000333889.5
REEP4	ENST00000523293.2	c.608G>C	p.Arg203Pro	missense_variant	Exon 7 of 7	3		ENSP00000428709.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.037
DANN	Benign	0.75
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.90	T
PhyloP100		-2.4
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.26
Sift	Benign	0.035	D
Sift4G	Uncertain	0.020	D
Vest4		0.060
MutPred		0.17		Loss of catalytic residue at S208 (P = 0.0094);
MVP		0.18
ClinPred		0.046	T
GERP RS		-11
Varity_R		0.083
Mutation Taster		=92/8	polymorphism

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: rs749573650; hg19: chr8-21996011;