NM_144967.4:c.1487-67G>A

Variant names:

• chrX-131088561-G-A
• rs3859991
• NM_144967.4:c.1487-67G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144967.4(ARHGAP36):​c.1487-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 1,119,907 control chromosomes in the GnomAD database, including 3,811 homozygotes. There are 30,232 hemizygotes in GnomAD. 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 0.085 (445 hom., 2910 hem., cov: 23)
  • Exomes 𝑓: 0.086 (3366 hom. 27322 hem.)
• Consequence: ARHGAP36 NM_144967.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• Publications: 1 publications found

Genes affected

ARHGAP36 (HGNC:26388): (Rho GTPase activating protein 36) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of catalytic activity and signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP36	NM_144967.4	c.1487-67G>A		intron_variant	Intron 11 of 11	ENST00000276211.10	NP_659404.2
ARHGAP36	NM_001282607.2	c.1451-67G>A		intron_variant	Intron 11 of 11		NP_001269536.1
ARHGAP36	NM_001330651.1	c.1079-67G>A		intron_variant	Intron 10 of 10		NP_001317580.1
ARHGAP36	XM_011531280.2	c.1079-67G>A		intron_variant	Intron 10 of 10		XP_011529582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP36	ENST00000276211.10	c.1487-67G>A		intron_variant	Intron 11 of 11	2	NM_144967.4	ENSP00000276211.5

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 9496 AN: 111822 Hom.: 442 Cov.: 23

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.0547

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0636

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.0858 AC: 86442 AN: 1008032 Hom.: 3366 AF XY: 0.0897 AC XY: 27322 AN XY: 304518

African (AFR) AF: 0.0603 AC: 1435 AN: 23794

American (AMR) AF: 0.320 AC: 8774 AN: 27403

Ashkenazi Jewish (ASJ) AF: 0.0589 AC: 1066 AN: 18095

East Asian (EAS) AF: 0.0996 AC: 2912 AN: 29229

South Asian (SAS) AF: 0.168 AC: 8064 AN: 48122

European-Finnish (FIN) AF: 0.0699 AC: 2552 AN: 36524

Middle Eastern (MID) AF: 0.0830 AC: 224 AN: 2699

European-Non Finnish (NFE) AF: 0.0731 AC: 56946 AN: 779386

Other (OTH) AF: 0.104 AC: 4469 AN: 42780

GnomAD4 genome AF: 0.0850 AC: 9514 AN: 111875 Hom.: 445 Cov.: 23 AF XY: 0.0854 AC XY: 2910 AN XY: 34073

African (AFR) AF: 0.0558 AC: 1721 AN: 30837

American (AMR) AF: 0.229 AC: 2434 AN: 10629

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 145 AN: 2651

East Asian (EAS) AF: 0.117 AC: 410 AN: 3516

South Asian (SAS) AF: 0.166 AC: 444 AN: 2671

European-Finnish (FIN) AF: 0.0658 AC: 398 AN: 6046

Middle Eastern (MID) AF: 0.0651 AC: 14 AN: 215

European-Non Finnish (NFE) AF: 0.0702 AC: 3732 AN: 53129

Other (OTH) AF: 0.119 AC: 179 AN: 1505

Alfa AF: 0.0768 Hom.: 487

Bravo AF: 0.0995

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.77
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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: rs3859991; hg19: chrX-130222535;