chr11-120211404-A-G

Position:

• chr11-120211404-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178507.4(OAF):​c.125A>G​(p.Gln42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,516,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: OAF NM_178507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

OAF (HGNC:28752): (out at first homolog)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0786258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAF	NM_178507.4	c.125A>G	p.Gln42Arg	missense_variant	1/4	ENST00000328965.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAF	ENST00000328965.9	c.125A>G	p.Gln42Arg	missense_variant	1/4	1	NM_178507.4	P1
OAF	ENST00000531220.1	c.-140A>G		5_prime_UTR_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152096 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000177 AC: 24 AN: 135494 Hom.: 0 AF XY: 0.000248 AC XY: 19 AN XY: 76500

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000461

Gnomad ASJ exome AF: 0.000136

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000347

Gnomad FIN exome AF: 0.000132

Gnomad NFE exome AF: 0.000232

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000204 AC: 278 AN: 1364708 Hom.: 0 Cov.: 25 AF XY: 0.000216 AC XY: 146 AN XY: 675866

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000903

Gnomad4 ASJ exome AF: 0.0000414

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000276

Gnomad4 FIN exome AF: 0.0000848

Gnomad4 NFE exome AF: 0.000224

Gnomad4 OTH exome AF: 0.000142

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152096 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74284

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000182 Hom.: 0

Bravo AF: 0.0000907

ExAC AF: 0.000188 AC: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.070
Sift	Benign	0.097	T
Sift4G	Benign	0.081	T
Polyphen		0.56	P
Vest4		0.28
MVP		0.39
MPC		0.56
ClinPred		0.046	T
GERP RS		4.5
Varity_R		0.18
gMVP		0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs752703302; hg19: chr11-120082112;