Genetic Variant LIN7A:c.82+1884T>A (chr12-80935757-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.200

Publications

60 publications found

Variant links:

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]

LIN7A links:

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]

MIR618 links:

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ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN7A	NM_004664.4 link	c.82+1884T>A		intron_variant	Intron 1 of 5	ENST00000552864.6	NP_004655.1	O14910

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LIN7A	ENST00000552864.6 link	c.82+1884T>A	intron_variant	Intron 1 of 5	1	NM_004664.4	ENSP00000447488.1	O14910
LIN7A	ENST00000549417.5 link	c.64+1884T>A	intron_variant	Intron 1 of 4	1		ENSP00000448975.1	H0YIA8
LIN7A	ENST00000261203.7 link	n.82+1884T>A	intron_variant	Intron 1 of 6	1		ENSP00000261203.3	J3KN23
MIR618	ENST00000385287.1 link	n.77T>A	non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

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:

AN:

349162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

197482

African (AFR)

AF:

0.00

AC:

AN:

10178

American (AMR)

AF:

0.00

AC:

AN:

35970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11104

East Asian (EAS)

AF:

0.00

AC:

AN:

12536

South Asian (SAS)

AF:

0.00

AC:

AN:

64222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

166278

Other (OTH)

AF:

0.00

AC:

AN:

15016

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.8

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over