NM_018948.4:c.730C>A

Variant names:

• chr1-8013869-G-T
• rs35110052
• NM_018948.4:c.730C>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_018948.4(ERRFI1):​c.730C>A​(p.Arg244Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00432 in 1,614,028 control chromosomes in the GnomAD database, including 218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (122 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (96 hom.)
• Consequence: ERRFI1 NM_018948.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.52
• Publications: 3 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-8013869-G-T is Benign according to our data. Variant chr1-8013869-G-T is described in ClinVar as Benign. ClinVar VariationId is 789687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

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.730C>A	p.Arg244Arg	synonymous	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.730C>A	p.Arg244Arg	synonymous	Exon 4 of 4	ENSP00000366702.5	Q9UJM3
	ERRFI1	ENST00000857115.1		c.730C>A	p.Arg244Arg	synonymous	Exon 5 of 5	ENSP00000527174.1
	ERRFI1	ENST00000857116.1		c.730C>A	p.Arg244Arg	synonymous	Exon 5 of 5	ENSP00000527175.1

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3350 AN: 152078 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.00588 AC: 1477 AN: 251246 AF XY: 0.00418

Gnomad AFR exome AF: 0.0741

Gnomad AMR exome AF: 0.00573

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000422

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00248 AC: 3625 AN: 1461832 Hom.: 96 Cov.: 31 AF XY: 0.00217 AC XY: 1578 AN XY: 727214

African (AFR) AF: 0.0747 AC: 2500 AN: 33480

American (AMR) AF: 0.00635 AC: 284 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86246

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5768

European-Non Finnish (NFE) AF: 0.000418 AC: 465 AN: 1111986

Other (OTH) AF: 0.00535 AC: 323 AN: 60390

GnomAD4 genome AF: 0.0220 AC: 3351 AN: 152196 Hom.: 122 Cov.: 32 AF XY: 0.0208 AC XY: 1546 AN XY: 74406

African (AFR) AF: 0.0746 AC: 3098 AN: 41510

American (AMR) AF: 0.0111 AC: 169 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000574 AC: 39 AN: 67996

Other (OTH) AF: 0.0203 AC: 43 AN: 2114

Alfa AF: 0.00984 Hom.: 31

Bravo AF: 0.0243

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.3
DANN	Benign	0.90
PhyloP100		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=84/16	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: rs35110052; hg19: chr1-8073929;