11-46680539-C-T

Variant names:

• chr11-46680539-C-T
• rs2064517044
• NM_004308.5:c.768G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004308.5(ARHGAP1):​c.768G>A​(p.Gln256Gln) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP1 NM_004308.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0190

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 11-46680539-C-T is Benign according to our data. Variant chr11-46680539-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 932503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.019 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP1	NM_004308.5	c.768G>A	p.Gln256Gln	synonymous_variant	Exon 9 of 13	ENST00000311956.9	NP_004299.1
ARHGAP1	XM_047426933.1	c.768G>A	p.Gln256Gln	synonymous_variant	Exon 9 of 13		XP_047282889.1
ARHGAP1	XM_024448520.2	c.636G>A	p.Gln212Gln	synonymous_variant	Exon 8 of 12		XP_024304288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP1	ENST00000311956.9	c.768G>A	p.Gln256Gln	synonymous_variant	Exon 9 of 13	1	NM_004308.5	ENSP00000310491.4
ARHGAP1	ENST00000526423.1	n.456G>A		non_coding_transcript_exon_variant	Exon 4 of 8	1
ARHGAP1	ENST00000528837.5	c.627G>A	p.Gln209Gln	synonymous_variant	Exon 7 of 11	5		ENSP00000434883.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.8
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs2064517044; hg19: chr11-46702089;