Genetic Variant NM_018362.4:c.157-73C>A (chr11-27501639-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018362.4(LIN7C):c.157-73C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,071,410 control chromosomes in the GnomAD database, including 292,908 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 0.68 ( 36210 hom., cov: 32)

Exomes 𝑓: 0.74 ( 256698 hom. )

Consequence

LIN7C
NM_018362.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.541

Publications

6 publications found

Variant links:

Genes affected

LIN7C (HGNC:17789): (lin-7 homolog C, crumbs cell polarity complex component) Enables L27 domain binding activity and cytoskeletal protein binding activity. Involved in morphogenesis of an epithelial sheet. Located in cell-cell junction; cytoplasm; and plasma membrane. Part of MPP7-DLG1-LIN7 complex. [provided by Alliance of Genome Resources, Apr 2022]

LIN7C links:

LGR4-AS1 (HGNC:40629): (LGR4 antisense RNA 1)

LGR4-AS1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIN7C	NM_018362.4 link	c.157-73C>A		intron_variant	Intron 2 of 4	ENST00000278193.7	NP_060832.1	Q9NUP9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LIN7C	ENST00000278193.7 link	c.157-73C>A	intron_variant	Intron 2 of 4	1	NM_018362.4	ENSP00000278193.2	Q9NUP9
LIN7C	ENST00000524596.1 link	c.156+163C>A	intron_variant	Intron 2 of 3	1		ENSP00000435353.1	G3V1D4
LGR4-AS1	ENST00000715842.1 link	n.432-11362G>T	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103374

AN:

151838

Hom.:

36211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.526

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.816

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.798

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.767

Gnomad OTH

AF:

0.690

GnomAD4 exome

AF:

0.743

AC:

683433

AN:

919454

Hom.:

256698

Cov.:

AF XY:

0.748

AC XY:

352609

AN XY:

471306

show subpopulations

African (AFR)

AF:

0.510

AC:

10723

AN:

21032

American (AMR)

AF:

0.543

AC:

14844

AN:

27312

Ashkenazi Jewish (ASJ)

AF:

0.815

AC:

16010

AN:

19636

East Asian (EAS)

AF:

0.545

AC:

19712

AN:

36200

South Asian (SAS)

AF:

0.800

AC:

51657

AN:

64580

European-Finnish (FIN)

AF:

0.749

AC:

38083

AN:

50844

Middle Eastern (MID)

AF:

0.758

AC:

3448

AN:

4548

European-Non Finnish (NFE)

AF:

0.762

AC:

498375

AN:

653824

Other (OTH)

AF:

0.737

AC:

30581

AN:

41478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

7784

15568

23352

31136

38920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.680

AC:

103385

AN:

151956

Hom.:

36210

Cov.:

AF XY:

0.683

AC XY:

50697

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.525

AC:

21736

AN:

41428

American (AMR)

AF:

0.624

AC:

9525

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.816

AC:

2831

AN:

3468

East Asian (EAS)

AF:

0.579

AC:

2997

AN:

5172

South Asian (SAS)

AF:

0.798

AC:

3846

AN:

4818

European-Finnish (FIN)

AF:

0.752

AC:

7930

AN:

10540

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.767

AC:

52089

AN:

67952

Other (OTH)

AF:

0.691

AC:

1455

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1554

3107

4661

6214

7768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.682

Hom.:

22132

Asia WGS

AF:

0.685

AC:

2378

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.9

(source)

DANN

Benign

0.53

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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NM_018362.4:c.157-73C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over