Genetic Variant NM_022165.3:c.37+8T>C (chr19-49114449-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022165.3(LIN7B):c.37+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,206,518 control chromosomes in the GnomAD database, including 85,062 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11626 hom., cov: 34)

Exomes 𝑓: 0.37 ( 73436 hom. )

Consequence

LIN7B
NM_022165.3 splice_region, intron

Scores

Splicing: ADA: 0.0001044

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.05

Publications

8 publications found

Variant links:

Genes affected

LIN7B (HGNC:17788): (lin-7 homolog B, crumbs cell polarity complex component) Enables protein domain specific binding activity. Predicted to be involved in maintenance of epithelial cell apical/basal polarity; neurotransmitter secretion; and protein localization to basolateral plasma membrane. Predicted to be located in plasma membrane. Predicted to be part of MPP7-DLG1-LIN7 complex. Predicted to be active in basolateral plasma membrane; cell-cell junction; and synapse. [provided by Alliance of Genome Resources, Apr 2022]

LIN7B links:

ENSG00000297778 (HGNC:):

ENSG00000297778 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 19-49114449-T-C is Benign according to our data. Variant chr19-49114449-T-C is described in ClinVar as Benign. ClinVar VariationId is 1279757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022165.3. 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
	LIN7B	NM_022165.3	MANE Select	c.37+8T>C		splice_region intron	N/A	NP_071448.1	Q9HAP6-1
	LIN7B	NM_001308419.2		c.37+8T>C		splice_region intron	N/A	NP_001295348.1	Q9HAP6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LIN7B	ENST00000221459.7	TSL:1 MANE Select	c.37+8T>C	splice_region intron	N/A	ENSP00000221459.2	Q9HAP6-1
LIN7B	ENST00000882750.1		c.37+8T>C	splice_region intron	N/A	ENSP00000552809.1
LIN7B	ENST00000391864.7	TSL:3	c.37+8T>C	splice_region intron	N/A	ENSP00000375737.3	Q9HAP6-2

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58413

AN:

151460

Hom.:

11606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.394

GnomAD2 exomes

AF:

0.00

AC:

AN:

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

GnomAD4 exome

AF:

0.371

AC:

391866

AN:

1054952

Hom.:

73436

Cov.:

AF XY:

0.372

AC XY:

185448

AN XY:

497900

show subpopulations

African (AFR)

AF:

0.458

AC:

10062

AN:

21960

American (AMR)

AF:

0.418

AC:

3146

AN:

7518

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

5517

AN:

13096

East Asian (EAS)

AF:

0.213

AC:

5142

AN:

24142

South Asian (SAS)

AF:

0.422

AC:

8140

AN:

19296

European-Finnish (FIN)

AF:

0.287

AC:

5921

AN:

20656

Middle Eastern (MID)

AF:

0.392

AC:

1086

AN:

2770

European-Non Finnish (NFE)

AF:

0.373

AC:

337154

AN:

903770

Other (OTH)

AF:

0.376

AC:

15698

AN:

41744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

11068

22137

33205

44274

55342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12574

25148

37722

50296

62870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.386

AC:

58473

AN:

151566

Hom.:

11626

Cov.:

AF XY:

0.380

AC XY:

28135

AN XY:

74064

show subpopulations

African (AFR)

AF:

0.448

AC:

18557

AN:

41402

American (AMR)

AF:

0.378

AC:

5759

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1482

AN:

3466

East Asian (EAS)

AF:

0.207

AC:

1060

AN:

5118

South Asian (SAS)

AF:

0.422

AC:

2036

AN:

4830

European-Finnish (FIN)

AF:

0.285

AC:

2977

AN:

10450

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.375

AC:

25397

AN:

67756

Other (OTH)

AF:

0.394

AC:

830

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1864

3728

5591

7455

9319

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.373

Hom.:

1316

Bravo

AF:

0.399

Asia WGS

AF:

0.336

AC:

1099

AN:

3270

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

LIN7B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

-1.1

PromoterAI

-0.098

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over