chr4-8009080-C-A

Variant names:

• chr4-8009080-C-A
• rs1311703718
• NM_001130083.2:c.1446G>T

Variant summary

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

The NM_001130083.2(ABLIM2):​c.1446G>T​(p.Glu482Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ABLIM2 NM_001130083.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.379
• Publications: 0 publications found

Genes affected

ABLIM2 (HGNC:19195): (actin binding LIM protein family member 2) Predicted to enable actin filament binding activity. Predicted to be involved in lamellipodium assembly. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

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=0.21571851).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130083.2. 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
	ABLIM2	NM_001130083.2	MANE Select	c.1446G>T	p.Glu482Asp	missense	Exon 15 of 21	NP_001123555.1	A0A140VK02
	ABLIM2	NM_001130084.2		c.1347G>T	p.Glu449Asp	missense	Exon 14 of 20	NP_001123556.1	Q6H8Q1-1
	ABLIM2	NM_001130085.2		c.1347G>T	p.Glu449Asp	missense	Exon 14 of 18	NP_001123557.1	Q6H8Q1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABLIM2	ENST00000447017.7	TSL:1 MANE Select	c.1446G>T	p.Glu482Asp	missense	Exon 15 of 21	ENSP00000393511.2	Q6H8Q1-9
	ABLIM2	ENST00000341937.9	TSL:1	c.1347G>T	p.Glu449Asp	missense	Exon 14 of 20	ENSP00000342813.5	Q6H8Q1-1
	ABLIM2	ENST00000361581.9	TSL:1	c.1347G>T	p.Glu449Asp	missense	Exon 14 of 18	ENSP00000355003.5	Q6H8Q1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461708 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727136

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60372

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.087
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.88	L
PhyloP100		0.38
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.048
Sift	Benign	0.21	T
Sift4G	Benign	0.23	T
Polyphen		0.0030	B
Vest4		0.32
MutPred		0.33		Gain of glycosylation at S446 (P = 0.0048)
MVP		0.65
MPC		0.082
ClinPred		0.94	D
GERP RS		2.0
Varity_R		0.065
gMVP		0.30
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1311703718; hg19: chr4-8010807;