11-46679215-T-C

Variant names:

• chr11-46679215-T-C
• rs200846104
• NM_004308.5:c.1142A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004308.5(ARHGAP1):​c.1142A>G​(p.His381Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000257 in 1,601,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: ARHGAP1 NM_004308.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08
• Publications: 3 publications found

Genes affected

ARHGAP1 (HGNC:673): (Rho GTPase activating protein 1) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein contains a SRC homology 3 domain and interacts with Bcl-2-associated protein family members. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.099618584).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004308.5. 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
	ARHGAP1	NM_004308.5	MANE Select	c.1142A>G	p.His381Arg	missense	Exon 13 of 13	NP_004299.1	Q07960

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP1	ENST00000311956.9	TSL:1 MANE Select	c.1142A>G	p.His381Arg	missense	Exon 13 of 13	ENSP00000310491.4	Q07960
	ARHGAP1	ENST00000526423.1	TSL:1	n.885A>G		non_coding_transcript_exon	Exon 8 of 8
	ARHGAP1	ENST00000873835.1		c.1307A>G	p.His436Arg	missense	Exon 13 of 13	ENSP00000543894.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.0000920 AC: 22 AN: 239076 AF XY: 0.0000777

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000268 AC: 388 AN: 1449048 Hom.: 0 Cov.: 32 AF XY: 0.000272 AC XY: 196 AN XY: 719510

African (AFR) AF: 0.0000301 AC: 1 AN: 33186

American (AMR) AF: 0.00 AC: 0 AN: 43610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 84576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.000328 AC: 362 AN: 1104674

Other (OTH) AF: 0.000418 AC: 25 AN: 59790

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68032

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000265 Hom.: 1

Bravo AF: 0.000200

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000107 AC: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.83	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.22
MVP		0.34
MPC		0.32
ClinPred		0.092	T
GERP RS		4.2
Varity_R		0.43
gMVP		0.29
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200846104; hg19: chr11-46700765;