10-133626710-G-C

Variant names:

• chr10-133626710-G-C
• rs75987380
• NM_001080998.2:c.33C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001080998.2(FRG2B):​c.33C>G​(p.His11Gln) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H11Y) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FRG2B NM_001080998.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.842
• Publications: 9 publications found

Genes affected

FRG2B (HGNC:33518): (FSHD region gene 2 family member B) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288107 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.002190113).
• BP6: Variant 10-133626710-G-C is Benign according to our data. Variant chr10-133626710-G-C is described in ClinVar as [Benign]. Clinvar id is 402880.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRG2B	NM_001080998.2	c.33C>G	p.His11Gln	missense_variant	Exon 1 of 4	ENST00000425520.2	NP_001074467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRG2B	ENST00000425520.2	c.33C>G	p.His11Gln	missense_variant	Exon 1 of 4	1	NM_001080998.2	ENSP00000401310.1
FRG2B	ENST00000443774.5	c.33C>G	p.His11Gln	missense_variant	Exon 1 of 4	1		ENSP00000408343.1
ENSG00000288107	ENST00000655152.1	n.446-823G>C		intron_variant	Intron 1 of 1
ENSG00000288107	ENST00000669404.1	n.303-823G>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.363 AC: 74483 AN: 205256 AF XY: 0.371

Gnomad AFR exome AF: 0.303

Gnomad AMR exome AF: 0.319

Gnomad ASJ exome AF: 0.387

Gnomad EAS exome AF: 0.277

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.382

Gnomad OTH exome AF: 0.308

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

Alfa AF: 0.178 Hom.: 0

ExAC AF: 0.491 AC: 59616

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.9
DANN	Benign	0.56
DEOGEN2	Benign	0.079	.;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.40	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	.;L
PhyloP100		0.84
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.046
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.077	.;B
Vest4		0.10
MutPred		0.095		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MPC		1.3
ClinPred		0.026	T
GERP RS		0.11
PromoterAI		-0.033	Neutral
Varity_R		0.28
gMVP		0.016
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: rs75987380; hg19: chr10-135440214; COSMIC: COSV71042476;