rs549746926

Variant names:

• chr9-35562463-T-C
• rs549746926
• NM_001164310.3:c.656A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164310.3(CIMIP2B):​c.656A>G​(p.Gln219Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,584,644 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (1 hom.)
• Consequence: CIMIP2B NM_001164310.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53
• Publications: 0 publications found

Genes affected

CIMIP2B (HGNC:34242): (ciliary microtubule inner protein 2B)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021916807).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164310.3. 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
	CIMIP2B	NM_001164310.3	MANE Select	c.656A>G	p.Gln219Arg	missense	Exon 5 of 6	NP_001157782.1	A8MTA8-1
	CIMIP2B	NM_001287239.2		c.610A>G	p.Arg204Gly	missense	Exon 5 of 6	NP_001274168.1
	CIMIP2B	NM_001287238.2		c.620A>G	p.Gln207Arg	missense	Exon 5 of 6	NP_001274167.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP2B	ENST00000399742.7	TSL:1 MANE Select	c.656A>G	p.Gln219Arg	missense	Exon 5 of 6	ENSP00000382646.2	A8MTA8-1
	CIMIP2B	ENST00000447837.1	TSL:1	c.588A>G	p.Pro196Pro	synonymous	Exon 5 of 6	ENSP00000412746.1	A8MTA8-2
	CIMIP2B	ENST00000492890.5	TSL:5	c.577A>G	p.Arg193Gly	missense	Exon 5 of 6	ENSP00000513459.1	A0A8V8TLC2

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00000482 AC: 1 AN: 207310 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000341

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000168 AC: 24 AN: 1432328 Hom.: 1 Cov.: 33 AF XY: 0.0000127 AC XY: 9 AN XY: 709402

African (AFR) AF: 0.00 AC: 0 AN: 32972

American (AMR) AF: 0.000323 AC: 13 AN: 40278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24634

East Asian (EAS) AF: 0.00 AC: 0 AN: 38998

South Asian (SAS) AF: 0.00 AC: 0 AN: 80244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1098152

Other (OTH) AF: 0.000168 AC: 10 AN: 59440

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.00105 AC: 16 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000359

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.5
DANN	Benign	0.83
DEOGEN2	Benign	0.00025	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.045
Sift	Benign	0.77	T
Sift4G	Benign	0.56	T
Polyphen		0.0070	B
Vest4		0.086
MutPred		0.12		Loss of ubiquitination at K222 (P = 0.0193)
MVP		0.067
MPC		0.053
ClinPred		0.45	T
GERP RS		2.1
Varity_R		0.054
gMVP		0.29
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs549746926; hg19: chr9-35562460;