16-281867-C-T

Variant names:

• chr16-281867-C-T
• rs149498191
• NM_001176.4:c.195C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001176.4(ARHGDIG):​c.195C>T​(p.Asp65Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,610,856 control chromosomes in the GnomAD database, including 60 homozygotes. 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 0.0035 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (59 hom.)
• Consequence: ARHGDIG NM_001176.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 3 publications found

Genes affected

ARHGDIG (HGNC:680): (Rho GDP dissociation inhibitor gamma) The GDP-dissociation inhibitors (GDIs) play a primary role in modulating the activation of GTPases by inhibiting the exchange of GDP for GTP. See ARHGDIB (MIM 602843).[supplied by OMIM, Nov 2010]

ENSG00000286901 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-2.39 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 59 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001176.4. 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
	ARHGDIG	NM_001176.4	MANE Select	c.195C>T	p.Asp65Asp	synonymous	Exon 2 of 6	NP_001167.2	Q99819

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGDIG	ENST00000219409.8	TSL:1 MANE Select	c.195C>T	p.Asp65Asp	synonymous	Exon 2 of 6	ENSP00000219409.3	Q99819
	ARHGDIG	ENST00000414650.1	TSL:3	c.-130C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000410541.1	C9J3B5
	ARHGDIG	ENST00000856700.1		c.237C>T	p.Asp79Asp	synonymous	Exon 2 of 6	ENSP00000526759.1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 535 AN: 152012 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00438

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00487 AC: 1179 AN: 242060 AF XY: 0.00547

Gnomad AFR exome AF: 0.000958

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.0315

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.000448

Gnomad NFE exome AF: 0.00369

Gnomad OTH exome AF: 0.00654

GnomAD4 exome AF: 0.00487 AC: 7110 AN: 1458726 Hom.: 59 Cov.: 32 AF XY: 0.00512 AC XY: 3719 AN XY: 725738

African (AFR) AF: 0.000597 AC: 20 AN: 33478

American (AMR) AF: 0.00219 AC: 98 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 856 AN: 26114

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39694

South Asian (SAS) AF: 0.0115 AC: 989 AN: 86252

European-Finnish (FIN) AF: 0.000396 AC: 20 AN: 50546

Middle Eastern (MID) AF: 0.00834 AC: 48 AN: 5756

European-Non Finnish (NFE) AF: 0.00420 AC: 4669 AN: 1111836

Other (OTH) AF: 0.00673 AC: 406 AN: 60352

GnomAD4 genome AF: 0.00352 AC: 536 AN: 152130 Hom.: 1 Cov.: 32 AF XY: 0.00335 AC XY: 249 AN XY: 74376

African (AFR) AF: 0.000940 AC: 39 AN: 41504

American (AMR) AF: 0.00307 AC: 47 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5154

South Asian (SAS) AF: 0.00705 AC: 34 AN: 4820

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00440 AC: 299 AN: 67986

Other (OTH) AF: 0.00190 AC: 4 AN: 2106

Alfa AF: 0.00567 Hom.: 3

Bravo AF: 0.00334

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00393

EpiControl AF: 0.00391

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.84
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs149498191; hg19: chr16-331867; COSMIC: COSV54731470; COSMIC: COSV54731470;