17-32021247-C-G

Variant names:

• chr17-32021247-C-G
• rs187030197
• ENST00000341671.12:c.101C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052888.3(LRRC37B):​c.101C>G​(p.Pro34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P34L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC37B NM_052888.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16805202).

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.1-146C>G		intron	N/A	NP_001308279.1	F5H5K1
	LRRC37B	NM_052888.3		c.101C>G	p.Pro34Arg	missense	Exon 1 of 12	NP_443120.2	Q96QE4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37B	ENST00000341671.12	TSL:1	c.101C>G	p.Pro34Arg	missense	Exon 1 of 12	ENSP00000340519.7	Q96QE4-1
	LRRC37B	ENST00000584368.5	TSL:1	c.101C>G	p.Pro34Arg	missense	Exon 1 of 10	ENSP00000463081.2	J3KTP0
	LRRC37B	ENST00000543378.7	TSL:2 MANE Select	c.1-146C>G		intron	N/A	ENSP00000443345.2	F5H5K1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251336 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460416 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726510

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4606

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60276

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.83
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.34
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.091	T
Polyphen		1.0	D
Vest4		0.077
MutPred		0.53		Loss of sheet (P = 0.0457)
MVP		0.15
MPC		0.29
ClinPred		0.59	D
GERP RS		0.77
PromoterAI		0.022	Neutral
Varity_R		0.094
gMVP		0.17

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: rs187030197; hg19: chr17-30348266;