11-47690661-C-T

Variant names:

• chr11-47690661-C-T
• rs7941404
• NM_024783.4:c.1046G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024783.4(AGBL2):​c.1046G>A​(p.Arg349His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,613,956 control chromosomes in the GnomAD database, including 13,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.092 (857 hom., cov: 31)
  • Exomes 𝑓: 0.12 (12466 hom.)
• Consequence: AGBL2 NM_024783.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

Genes affected

AGBL2 (HGNC:26296): (AGBL carboxypeptidase 2) Predicted to enable metallocarboxypeptidase activity. Predicted to be involved in protein side chain deglutamylation. Located in centriole and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015272796).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL2	NM_024783.4	c.1046G>A	p.Arg349His	missense_variant	Exon 10 of 19	ENST00000525123.6	NP_079059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL2	ENST00000525123.6	c.1046G>A	p.Arg349His	missense_variant	Exon 10 of 19	1	NM_024783.4	ENSP00000435582.1
AGBL2	ENST00000528244.5	c.932G>A	p.Arg311His	missense_variant	Exon 9 of 16	2		ENSP00000436630.1
AGBL2	ENST00000532595.5	c.878G>A	p.Arg293His	missense_variant	Exon 8 of 8	2		ENSP00000436063.1
AGBL2	ENST00000529712.5	n.1580G>A		non_coding_transcript_exon_variant	Exon 7 of 11	2

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13929 AN: 151996 Hom.: 857 Cov.: 31

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0815

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.106

GnomAD3 exomes AF: 0.0948 AC: 23827 AN: 251396 Hom.: 1507 AF XY: 0.0960 AC XY: 13040 AN XY: 135856

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.0604

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0368

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.123 AC: 180134 AN: 1461842 Hom.: 12466 Cov.: 32 AF XY: 0.121 AC XY: 88021 AN XY: 727232

Gnomad4 AFR exome AF: 0.0190

Gnomad4 AMR exome AF: 0.0630

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0379

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.0915 AC: 13926 AN: 152114 Hom.: 857 Cov.: 31 AF XY: 0.0877 AC XY: 6523 AN XY: 74362

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.0812

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0336

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.105

Alfa AF: 0.124 Hom.: 2464

Bravo AF: 0.0864

TwinsUK AF: 0.145 AC: 539

ALSPAC AF: 0.139 AC: 536

ESP6500AA AF: 0.0286 AC: 126

ESP6500EA AF: 0.139 AC: 1191

ExAC AF: 0.0943 AC: 11444

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.137

EpiControl AF: 0.138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.32
DANN	Benign	0.16
DEOGEN2	Benign	0.00055	T;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0092	N
MetaRNN	Benign	0.0015	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.77	N;.;.;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	1.2	N;N;N;N
REVEL	Benign	0.016
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.70	T;T;T;T
Polyphen		0.0040	B;.;B;.
Vest4		0.020
MPC		0.13
ClinPred		0.0054	T
GERP RS		-0.36
Varity_R		0.021
gMVP		0.17

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: rs7941404; hg19: chr11-47712213; COSMIC: COSV54092112; COSMIC: COSV54092112;