12-80935757-A-C

Variant names:

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

Variant summary

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

The NM_004664.4(LIN7A):​c.82+1884T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 500,570 control chromosomes in the GnomAD database, including 171,423 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 0.81 (50012 hom., cov: 31)
  • Exomes 𝑓: 0.83 (121411 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122677 AN: 151890 Hom.: 49990 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.843

GnomAD2 exomes AF: 0.833 AC: 208552 AN: 250244 AF XY: 0.829

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.927

Gnomad ASJ exome AF: 0.894

Gnomad EAS exome AF: 0.746

Gnomad FIN exome AF: 0.834

Gnomad NFE exome AF: 0.860

Gnomad OTH exome AF: 0.854

GnomAD4 exome AF: 0.831 AC: 289711 AN: 348562 Hom.: 121411 Cov.: 0 AF XY: 0.822 AC XY: 161976 AN XY: 197136

African (AFR) AF: 0.691 AC: 7021 AN: 10166

American (AMR) AF: 0.926 AC: 33314 AN: 35958

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 9943 AN: 11096

East Asian (EAS) AF: 0.748 AC: 9377 AN: 12528

South Asian (SAS) AF: 0.734 AC: 47034 AN: 64050

European-Finnish (FIN) AF: 0.833 AC: 25929 AN: 31110

Middle Eastern (MID) AF: 0.866 AC: 2332 AN: 2694

European-Non Finnish (NFE) AF: 0.857 AC: 142162 AN: 165966

Other (OTH) AF: 0.840 AC: 12599 AN: 14994

GnomAD4 genome AF: 0.808 AC: 122753 AN: 152008 Hom.: 50012 Cov.: 31 AF XY: 0.806 AC XY: 59902 AN XY: 74292

African (AFR) AF: 0.695 AC: 28789 AN: 41400

American (AMR) AF: 0.889 AC: 13585 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3095 AN: 3470

East Asian (EAS) AF: 0.727 AC: 3752 AN: 5164

South Asian (SAS) AF: 0.726 AC: 3495 AN: 4812

European-Finnish (FIN) AF: 0.834 AC: 8812 AN: 10560

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58438 AN: 68000

Other (OTH) AF: 0.843 AC: 1784 AN: 2116

Alfa AF: 0.835 Hom.: 105783

Bravo AF: 0.809

Asia WGS AF: 0.724 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.0
DANN	Benign	0.58
PhyloP100		-0.20
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: rs2682818; hg19: chr12-81329536; COSMIC: COSV54019323; COSMIC: COSV54019323;