11-122115732-A-G

Variant names:

• chr11-122115732-A-G
• rs756859038
• NM_001001786.3:c.191T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001786.3(BLID):​c.191T>C​(p.Val64Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. V64E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BLID NM_001001786.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 0 publications found

Genes affected

BLID (HGNC:33495): (BH3-like motif containing, cell death inducer) This gene encodes a BH3-like motif containing protein involved in cell death. The encoded protein may induce apoptosis in a caspase-dependent manner. The protein is localized in both the cytoplasm and the mitochondrion. [provided by RefSeq, Aug 2011]

MIR100HG (HGNC:39522): (mir-100-let-7a-2-mir-125b-1 cluster host gene) This gene produces long non-coding RNAs that act as regulators of cell proliferation. Alternative promoter usage and splicing results in multiple transcript variants. Some transcript variants may promote growth, while others may act to negatively regulate cell division. [provided by RefSeq, May 2016]

ENSG00000301769 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09667292).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001786.3. 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
	BLID	NM_001001786.3	MANE Select	c.191T>C	p.Val64Ala	missense	Exon 1 of 1	NP_001001786.2	Q8IZY5
	MIR100HG	NR_024430.2		n.492-23992T>C		intron	N/A
	MIR100HG	NR_137179.1		n.446-23992T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLID	ENST00000560104.2	TSL:6 MANE Select	c.191T>C	p.Val64Ala	missense	Exon 1 of 1	ENSP00000453153.1	Q8IZY5
	MIR100HG	ENST00000534782.4	TSL:1	n.388-24013T>C		intron	N/A
	MIR100HG	ENST00000534297.2	TSL:4	n.376+401T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.69
DEOGEN2	Benign	0.097	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.046
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.0	D
Polyphen		0.017	B
Vest4		0.17
MutPred		0.21		Gain of disorder (P = 0.0559)
MVP		0.81
MPC		0.061
ClinPred		0.074	T
GERP RS		-0.59
PromoterAI		0.0034	Neutral
Varity_R		0.40
gMVP		0.028
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs756859038; hg19: chr11-121986440; COSMIC: COSV73340254;