1-3463528-C-T

Variant names:

• chr1-3463528-C-T
• rs973644560
• NM_014448.4:c.444C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014448.4(ARHGEF16):​c.444C>T​(p.Asn148Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,320,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: ARHGEF16 NM_014448.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 0 publications found

Genes affected

ARHGEF16 (HGNC:15515): (Rho guanine nucleotide exchange factor 16) Although the specific function of this protein is not known yet, it is thought to be involved in protein-protein and protein-lipid interactions. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.005 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014448.4. 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
	ARHGEF16	NM_014448.4	MANE Select	c.444C>T	p.Asn148Asn	synonymous	Exon 2 of 15	NP_055263.2	Q5VV41-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF16	ENST00000378378.9	TSL:2 MANE Select	c.444C>T	p.Asn148Asn	synonymous	Exon 2 of 15	ENSP00000367629.4	Q5VV41-1
	ARHGEF16	ENST00000868563.1		c.444C>T	p.Asn148Asn	synonymous	Exon 2 of 17	ENSP00000538622.1
	ARHGEF16	ENST00000868561.1		c.444C>T	p.Asn148Asn	synonymous	Exon 2 of 15	ENSP00000538620.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1320796 Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1 AN XY: 643100

African (AFR) AF: 0.00 AC: 0 AN: 28936

American (AMR) AF: 0.00 AC: 0 AN: 23618

Ashkenazi Jewish (ASJ) AF: 0.0000503 AC: 1 AN: 19872

East Asian (EAS) AF: 0.00 AC: 0 AN: 35064

South Asian (SAS) AF: 0.00 AC: 0 AN: 67088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041376

Other (OTH) AF: 0.00 AC: 0 AN: 54486

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.7
DANN	Benign	0.46
PhyloP100		-0.0050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.4
Mutation Taster		=100/0	polymorphism

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: rs973644560; hg19: chr1-3380092;