chr11-46680720-C-T

Variant names:

• chr11-46680720-C-T
• rs1237956979
• NM_004308.5:c.663G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004308.5(ARHGAP1):​c.663G>A​(p.Gln221Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ARHGAP1 NM_004308.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 0 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.075).
• BP7: Synonymous conserved (PhyloP=1.89 with no splicing effect.

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.663G>A	p.Gln221Gln	synonymous	Exon 8 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.663G>A	p.Gln221Gln	synonymous	Exon 8 of 13	ENSP00000310491.4	Q07960
	ARHGAP1	ENST00000526423.1	TSL:1	n.351G>A		non_coding_transcript_exon	Exon 3 of 8
	ARHGAP1	ENST00000873835.1		c.828G>A	p.Gln276Gln	synonymous	Exon 8 of 13	ENSP00000543894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 205800 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1413792 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 698458

African (AFR) AF: 0.00 AC: 0 AN: 32232

American (AMR) AF: 0.00 AC: 0 AN: 39154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22594

East Asian (EAS) AF: 0.00 AC: 0 AN: 39354

South Asian (SAS) AF: 0.00 AC: 0 AN: 78344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089010

Other (OTH) AF: 0.00 AC: 0 AN: 58278

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	9.9
DANN	Benign	0.74
PhyloP100		1.9

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: rs1237956979; hg19: chr11-46702270;