chr8-93734247-G-C

Variant names:

• chr8-93734247-G-C
• rs754057902
• NM_001377960.1:c.2164C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001377960.1(RBM12B):​c.2164C>G​(p.His722Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H722Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RBM12B NM_001377960.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 publications found

Genes affected

RBM12B (HGNC:32310): (RNA binding motif protein 12B) Enables RNA binding activity. Predicted to be involved in regulation of RNA splicing. Predicted to be part of ribonucleoprotein complex. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253722 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03717822).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377960.1. 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
	RBM12B	NM_001377960.1	MANE Select	c.2164C>G	p.His722Asp	missense	Exon 4 of 4	NP_001364889.1	Q8IXT5
	RBM12B	NM_001377961.1		c.2164C>G	p.His722Asp	missense	Exon 5 of 5	NP_001364890.1	Q8IXT5
	RBM12B	NM_001377962.1		c.2164C>G	p.His722Asp	missense	Exon 3 of 3	NP_001364891.1	Q8IXT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM12B	ENST00000520560.6	TSL:2 MANE Select	c.2164C>G	p.His722Asp	missense	Exon 4 of 4	ENSP00000429807.2	Q8IXT5
	RBM12B	ENST00000517700.6	TSL:1	c.2164C>G	p.His722Asp	missense	Exon 3 of 3	ENSP00000427729.2	Q8IXT5
	RBM12B	ENST00000399300.7	TSL:2	c.2164C>G	p.His722Asp	missense	Exon 3 of 3	ENSP00000382239.2	Q8IXT5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458886 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 725600

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.00 AC: 0 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25786

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110582

Other (OTH) AF: 0.00 AC: 0 AN: 60192

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.4
DANN	Benign	0.80
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.029
Sift	Benign	0.49	T
Sift4G	Benign	0.91	T
Polyphen		0.0	B
Vest4		0.060
MutPred		0.22		Loss of helix (P = 0.028)
MVP		0.29
ClinPred		0.046	T
GERP RS		2.3
Varity_R		0.056
gMVP		0.12
Mutation Taster		=96/4	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: rs754057902; hg19: chr8-94746475;