7-144187100-G-A

Position:

• chr7-144187100-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The ENST00000378115.3(ARHGEF35):​c.1284C>T​(p.Leu428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.0017 (6 hom., cov: 20)
  • Exomes 𝑓: 0.0023 (471 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF35 ENST00000378115.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.327

Genes affected

ARHGEF35 (HGNC:33846): (Rho guanine nucleotide exchange factor 35)

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=0.327 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF35	NM_001003702.3	c.1284C>T	p.Leu428=	synonymous_variant	2/2	ENST00000378115.3	NP_001003702.2
ARHGEF35	NM_001368318.1	c.1284C>T	p.Leu428=	synonymous_variant	2/2		NP_001355247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF35	ENST00000378115.3	c.1284C>T	p.Leu428=	synonymous_variant	2/2	1	NM_001003702.3	ENSP00000367355	P1
ARHGEF35	ENST00000688754.1	c.1284C>T	p.Leu428=	synonymous_variant	2/2			ENSP00000510684	P1

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 227 AN: 132238 Hom.: 6 Cov.: 20

Gnomad AFR AF: 0.000307

Gnomad AMI AF: 0.00583

Gnomad AMR AF: 0.00193

Gnomad ASJ AF: 0.00774

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000456

Gnomad FIN AF: 0.000919

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.00170

GnomAD3 exomes AF: 0.000729 AC: 161 AN: 220846 Hom.: 9 AF XY: 0.000657 AC XY: 79 AN XY: 120276

Gnomad AFR exome AF: 0.000159

Gnomad AMR exome AF: 0.000431

Gnomad ASJ exome AF: 0.00307

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.000864

Gnomad OTH exome AF: 0.000739

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00234 AC: 3215 AN: 1372676 Hom.: 471 Cov.: 31 AF XY: 0.00230 AC XY: 1575 AN XY: 683604

Gnomad4 AFR exome AF: 0.000467

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.00750

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000190

Gnomad4 FIN exome AF: 0.00196

Gnomad4 NFE exome AF: 0.00260

Gnomad4 OTH exome AF: 0.00218

GnomAD4 genome AF: 0.00172 AC: 227 AN: 132348 Hom.: 6 Cov.: 20 AF XY: 0.00169 AC XY: 109 AN XY: 64590

Gnomad4 AFR AF: 0.000306

Gnomad4 AMR AF: 0.00192

Gnomad4 ASJ AF: 0.00774

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000457

Gnomad4 FIN AF: 0.000919

Gnomad4 NFE AF: 0.00251

Gnomad4 OTH AF: 0.00168

Alfa AF: 0.00309 Hom.: 6

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

ARHGEF35: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.90

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: rs201754709; hg19: chr7-143884193; COSMIC: COSV104688431; COSMIC: COSV104688431;