1-8013327-C-A

Variant names:

• chr1-8013327-C-A
• rs757532406
• NM_018948.4:c.1272G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018948.4(ERRFI1):​c.1272G>T​(p.Gln424His) 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. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q424K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERRFI1 NM_018948.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 1 publications found

Genes affected

ERRFI1 (HGNC:18185): (ERBB receptor feedback inhibitor 1) ERRFI1 is a cytoplasmic protein whose expression is upregulated with cell growth (Wick et al., 1995 [PubMed 7641805]). It shares significant homology with the protein product of rat gene-33, which is induced during cell stress and mediates cell signaling (Makkinje et al., 2000 [PubMed 10749885]; Fiorentino et al., 2000 [PubMed 11003669]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13290146).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018948.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERRFI1	NM_018948.4	MANE Select	c.1272G>T	p.Gln424His	missense	Exon 4 of 4	NP_061821.1	I6S2Y9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERRFI1	ENST00000377482.10	TSL:1 MANE Select	c.1272G>T	p.Gln424His	missense	Exon 4 of 4	ENSP00000366702.5	Q9UJM3
	ERRFI1	ENST00000857115.1		c.1272G>T	p.Gln424His	missense	Exon 5 of 5	ENSP00000527174.1
	ERRFI1	ENST00000857116.1		c.1272G>T	p.Gln424His	missense	Exon 5 of 5	ENSP00000527175.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.015
Sift	Benign	0.066	T
Sift4G	Benign	0.19	T
Polyphen		0.012	B
Vest4		0.086
MutPred		0.30		Loss of disorder (P = 0.1067)
MVP		0.36
MPC		0.16
ClinPred		0.12	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.34
Mutation Taster		=77/23	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: rs757532406; hg19: chr1-8073387;