dbSNP rs17325887: LRRC7:c.303+97T>C (chr1-69760490-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001370785.2(LRRC7):c.303+97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0285 in 978,586 control chromosomes in the GnomAD database, including 491 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 0.031 ( 78 hom., cov: 32)

Exomes 𝑓: 0.028 ( 413 hom. )

Consequence

LRRC7
NM_001370785.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

Publications

6 publications found

Variant links:

Genes affected

LRRC7 (HGNC:18531): (leucine rich repeat containing 7) Predicted to be involved in several processes, including establishment or maintenance of epithelial cell apical/basal polarity; positive regulation of neuron projection development; and receptor clustering. Located in several cellular components, including centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRRC7 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

LRRC7 links:

LOC124904199 (HGNC:):

LOC124904199 links:

Genome browser will be placed here

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=-0.86).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0307 (4673/152136) while in subpopulation AFR AF = 0.046 (1912/41534). AF 95% confidence interval is 0.0443. There are 78 homozygotes in GnomAd4. There are 2239 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4673 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC7	NM_001370785.2 link	c.303+97T>C		intron_variant	Intron 3 of 26	ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2 link	c.303+97T>C		intron_variant	Intron 3 of 26		NM_001370785.2	ENSP00000498937.2		A0A494C1A4

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4678

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0462

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.0226

Gnomad SAS

AF:

0.0364

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0292

Gnomad OTH

AF:

0.0325

GnomAD4 exome

AF:

0.0280

AC:

23179

AN:

826450

Hom.:

413

AF XY:

0.0284

AC XY:

12071

AN XY:

424584

show subpopulations

African (AFR)

AF:

0.0473

AC:

915

AN:

19344

American (AMR)

AF:

0.00876

AC:

259

AN:

29578

Ashkenazi Jewish (ASJ)

AF:

0.0177

AC:

336

AN:

18996

East Asian (EAS)

AF:

0.0231

AC:

760

AN:

32926

South Asian (SAS)

AF:

0.0362

AC:

2193

AN:

60662

European-Finnish (FIN)

AF:

0.0148

AC:

692

AN:

46666

Middle Eastern (MID)

AF:

0.0307

AC:

126

AN:

4102

European-Non Finnish (NFE)

AF:

0.0294

AC:

16903

AN:

575866

Other (OTH)

AF:

0.0260

AC:

995

AN:

38310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1147

2294

3441

4588

5735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

472

944

1416

1888

2360

<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:

0.0307

AC:

4673

AN:

152136

Hom.:

Cov.:

AF XY:

0.0301

AC XY:

2239

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0460

AC:

1912

AN:

41534

American (AMR)

AF:

0.0130

AC:

199

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3462

East Asian (EAS)

AF:

0.0226

AC:

117

AN:

5166

South Asian (SAS)

AF:

0.0364

AC:

176

AN:

4830

European-Finnish (FIN)

AF:

0.0146

AC:

155

AN:

10622

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0292

AC:

1982

AN:

67938

Other (OTH)

AF:

0.0322

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

226

452

677

903

1129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0304

Hom.:

135

Bravo

AF:

0.0299

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

-0.0030

PromoterAI

-0.029

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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