4-8005201-C-T

Variant names:

• chr4-8005201-C-T
• rs11939078
• NM_001130083.2:c.1618+2858G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130083.2(ABLIM2):​c.1618+2858G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 437,630 control chromosomes in the GnomAD database, including 15,443 homozygotes. 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: 𝑓 0.25 (5076 hom., cov: 33)
  • Exomes 𝑓: 0.26 (10367 hom.)
• Consequence: ABLIM2 NM_001130083.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 5 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]

MIR95 (HGNC:31647): (microRNA 95) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABLIM2	NM_001130083.2	c.1618+2858G>A		intron_variant	Intron 16 of 20	ENST00000447017.7	NP_001123555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABLIM2	ENST00000447017.7	c.1618+2858G>A		intron_variant	Intron 16 of 20	1	NM_001130083.2	ENSP00000393511.2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38094 AN: 152118 Hom.: 5080 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.264 AC: 75219 AN: 285394 Hom.: 10367 AF XY: 0.261 AC XY: 41277 AN XY: 158034

African (AFR) AF: 0.185 AC: 1574 AN: 8524

American (AMR) AF: 0.136 AC: 3701 AN: 27294

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 2527 AN: 7564

East Asian (EAS) AF: 0.239 AC: 2721 AN: 11362

South Asian (SAS) AF: 0.231 AC: 12532 AN: 54178

European-Finnish (FIN) AF: 0.240 AC: 4580 AN: 19068

Middle Eastern (MID) AF: 0.282 AC: 252 AN: 894

European-Non Finnish (NFE) AF: 0.305 AC: 43905 AN: 143802

Other (OTH) AF: 0.270 AC: 3427 AN: 12708

GnomAD4 genome AF: 0.250 AC: 38085 AN: 152236 Hom.: 5076 Cov.: 33 AF XY: 0.244 AC XY: 18137 AN XY: 74436

African (AFR) AF: 0.186 AC: 7726 AN: 41558

American (AMR) AF: 0.183 AC: 2797 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3472

East Asian (EAS) AF: 0.239 AC: 1238 AN: 5182

South Asian (SAS) AF: 0.219 AC: 1058 AN: 4826

European-Finnish (FIN) AF: 0.226 AC: 2396 AN: 10594

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20861 AN: 67982

Other (OTH) AF: 0.248 AC: 525 AN: 2116

Alfa AF: 0.281 Hom.: 2093

Bravo AF: 0.244

Asia WGS AF: 0.209 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.82
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs11939078; hg19: chr4-8006928; COSMIC: COSV56403353; COSMIC: COSV56403353;