rs10521205

Variant names:

• chr17-12965825-T-C
• rs10521205
• NM_014859.6:c.1523+6928T>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.1523+6928T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,194 control chromosomes in the GnomAD database, including 894 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 0.10 (894 hom., cov: 32)
• Consequence: ARHGAP44 NM_014859.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 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.1523+6928T>C		intron	N/A	NP_055674.4
	ARHGAP44	NM_001321166.2		c.1523+6928T>C		intron	N/A	NP_001308095.1	Q17R89-3
	ARHGAP44	NM_001321167.2		c.1523+6928T>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.1523+6928T>C		intron	N/A	ENSP00000368994.5	Q17R89-1
	ARHGAP44	ENST00000340825.7	TSL:1	c.1523+6928T>C		intron	N/A	ENSP00000342566.3	Q17R89-3
	ARHGAP44	ENST00000262444.13	TSL:1	c.1523+6928T>C		intron	N/A	ENSP00000262444.9	E7ERK8

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15258 AN: 152076 Hom.: 893 Cov.: 32

Gnomad AFR AF: 0.0685

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.100 AC: 15272 AN: 152194 Hom.: 894 Cov.: 32 AF XY: 0.0996 AC XY: 7413 AN XY: 74416

African (AFR) AF: 0.0686 AC: 2849 AN: 41520

American (AMR) AF: 0.0826 AC: 1263 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3470

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.202 AC: 973 AN: 4822

European-Finnish (FIN) AF: 0.0762 AC: 808 AN: 10600

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8308 AN: 68000

Other (OTH) AF: 0.115 AC: 242 AN: 2110

Alfa AF: 0.120 Hom.: 632

Bravo AF: 0.0987

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.35
PhyloP100		0.43
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: rs10521205; hg19: chr17-12869142; COSMIC: COSV52400918;