17-12917329-G-C

Variant names:

• chr17-12917329-G-C
• rs7210937
• NM_014859.6:c.387+1318G>C

Variant summary

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

The NM_014859.6(ARHGAP44):​c.387+1318G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 153,760 control chromosomes in the GnomAD database, including 6,805 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 0.23 (6790 hom., cov: 32)
  • Exomes 𝑓: 0.11 (15 hom.)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 13 publications found

Genes affected

ARHGAP44 (HGNC:29096): (Rho GTPase activating protein 44) Enables phospholipid binding activity. Predicted to be involved in several processes, including modification of dendritic spine; negative regulation of Rac protein signal transduction; and regulation of plasma membrane bounded cell projection organization. Located in leading edge membrane. [provided by Alliance of Genome Resources, Apr 2022]

MIR1269B (HGNC:41787): (microRNA 1269b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014859.6. 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
	ARHGAP44	NM_014859.6	MANE Select	c.387+1318G>C		intron	N/A	NP_055674.4
	ARHGAP44	NM_001321166.2		c.387+1318G>C		intron	N/A	NP_001308095.1	Q17R89-3
	ARHGAP44	NM_001321167.2		c.387+1318G>C		intron	N/A	NP_001308096.1	E7ERK8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP44	ENST00000379672.10	TSL:1 MANE Select	c.387+1318G>C		intron	N/A	ENSP00000368994.5	Q17R89-1
	ARHGAP44	ENST00000340825.7	TSL:1	c.387+1318G>C		intron	N/A	ENSP00000342566.3	Q17R89-3
	ARHGAP44	ENST00000262444.13	TSL:1	c.387+1318G>C		intron	N/A	ENSP00000262444.9	E7ERK8

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34243 AN: 151984 Hom.: 6769 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.0824 AC: 30 AN: 364 AF XY: 0.0750

Gnomad AFR exome AF: 0.500

Gnomad EAS exome AF: 0.00

Gnomad NFE exome AF: 0.0833

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.107 AC: 178 AN: 1658 Hom.: 15 Cov.: 0 AF XY: 0.109 AC XY: 103 AN XY: 948

African (AFR) AF: 0.367 AC: 22 AN: 60

American (AMR) AF: 0.286 AC: 4 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.500 AC: 9 AN: 18

South Asian (SAS) AF: 0.273 AC: 12 AN: 44

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.0920 AC: 71 AN: 772

European-Non Finnish (NFE) AF: 0.0639 AC: 39 AN: 610

Other (OTH) AF: 0.162 AC: 21 AN: 130

GnomAD4 genome AF: 0.226 AC: 34305 AN: 152102 Hom.: 6790 Cov.: 32 AF XY: 0.227 AC XY: 16865 AN XY: 74356

African (AFR) AF: 0.517 AC: 21424 AN: 41468

American (AMR) AF: 0.156 AC: 2382 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.431 AC: 2218 AN: 5146

South Asian (SAS) AF: 0.296 AC: 1424 AN: 4818

European-Finnish (FIN) AF: 0.0830 AC: 878 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0733 AC: 4983 AN: 68020

Other (OTH) AF: 0.184 AC: 387 AN: 2106

Alfa AF: 0.142 Hom.: 425

Bravo AF: 0.241

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.93
DANN	Benign	0.54
PhyloP100		-0.38
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: rs7210937; hg19: chr17-12820646;