12-80935757-A-T

Variant names:

• chr12-80935757-A-T
• rs2682818
• NM_004664.4:c.82+1884T>A

Variant summary

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

The NM_004664.4(LIN7A):​c.82+1884T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIN7A NM_004664.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 60 publications found

Genes affected

LIN7A (HGNC:17787): (lin-7 homolog A, crumbs cell polarity complex component) The protein encoded by this gene is involved in generating and maintaining the asymmetric distribution of channels and receptors at the cell membrane. The encoded protein also is required for the localization of some specific channels and can be part of a protein complex that couples synaptic vesicle exocytosis to cell adhesion in the brain. [provided by RefSeq, May 2016]

MIR618 (HGNC:32874): (microRNA 618) 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: 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 (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004664.4. 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
	LIN7A	NM_004664.4	MANE Select	c.82+1884T>A		intron	N/A	NP_004655.1	O14910
	LIN7A	NM_001324423.2		c.-13+1884T>A		intron	N/A	NP_001311352.1
	MIR618	NR_030349.1		n.77T>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIN7A	ENST00000552864.6	TSL:1 MANE Select	c.82+1884T>A		intron	N/A	ENSP00000447488.1	O14910
	LIN7A	ENST00000549417.5	TSL:1	c.64+1884T>A		intron	N/A	ENSP00000448975.1	H0YIA8
	LIN7A	ENST00000261203.7	TSL:1	n.82+1884T>A		intron	N/A	ENSP00000261203.3	J3KN23

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250244 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 349162 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 197482

African (AFR) AF: 0.00 AC: 0 AN: 10178

American (AMR) AF: 0.00 AC: 0 AN: 35970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11104

East Asian (EAS) AF: 0.00 AC: 0 AN: 12536

South Asian (SAS) AF: 0.00 AC: 0 AN: 64222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 166278

Other (OTH) AF: 0.00 AC: 0 AN: 15016

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.42
PhyloP100		-0.20

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: rs2682818; hg19: chr12-81329536;