Genetic Variant LRRC37B:p.Glu58Ala (chr17-32021319-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_052888.3(LRRC37B):c.173A>C(p.Glu58Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000295 in 1,613,738 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

LRRC37B
NM_052888.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.283

Publications

2 publications found

Variant links:

Genes affected

LRRC37B (HGNC:29070): (leucine rich repeat containing 37B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04294011).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052888.3. 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
	LRRC37B	NM_001321350.2	MANE Select	c.1-74A>C		intron	N/A	NP_001308279.1	F5H5K1
	LRRC37B	NM_052888.3		c.173A>C	p.Glu58Ala	missense	Exon 1 of 12	NP_443120.2	Q96QE4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC37B	ENST00000341671.12	TSL:1	c.173A>C	p.Glu58Ala	missense	Exon 1 of 12	ENSP00000340519.7	Q96QE4-1
LRRC37B	ENST00000584368.5	TSL:1	c.173A>C	p.Glu58Ala	missense	Exon 1 of 10	ENSP00000463081.2	J3KTP0
LRRC37B	ENST00000543378.7	TSL:2 MANE Select	c.1-74A>C		intron	N/A	ENSP00000443345.2	F5H5K1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000251

AC:

AN:

250924

AF XY:

0.000236

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000285

AC:

417

AN:

1461542

Hom.:

Cov.:

AF XY:

0.000304

AC XY:

221

AN XY:

727058

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00101

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.000314

AC:

349

AN:

1111922

Other (OTH)

AF:

0.000182

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

109

136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000388

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41522

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000779

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000708

Hom.:

Bravo

AF:

0.000196

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.37

CADD

Benign

3.8

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.041

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.50

M_CAP

Benign

0.015

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.6

PhyloP100

0.28

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.12

Sift

Uncertain

0.0070

Sift4G

Benign

0.11

Polyphen

0.89

Vest4

0.078

MVP

0.21

MPC

0.16

ClinPred

0.060

GERP RS

-2.3

PromoterAI

-0.0084

Neutral

(source)

Varity_R

0.11

gMVP

0.14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over