rs557815137

Variant names:

• chr17-46297471-G-C
• rs557815137
• NM_014834.4:c.2338G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014834.4(LRRC37A):​c.2338G>C​(p.Val780Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000060 (3 hom., cov: 18)
  • Exomes 𝑓: 0.00012 (40 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.200
• Publications: 0 publications found

Genes affected

LRRC37A (HGNC:29069): (leucine rich repeat containing 37A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17B (HGNC:32387): (ADP ribosylation factor like GTPase 17B) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0072587132).
• BP6: Variant 17-46297471-G-C is Benign according to our data. Variant chr17-46297471-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3120581.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014834.4. 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
	LRRC37A	NM_014834.4	MANE Select	c.2338G>C	p.Val780Leu	missense	Exon 1 of 14	NP_055649.4	A6NMS7
	ARL17B	NM_001103154.2		c.*21+2055C>G		intron	N/A	NP_001096624.1
	ARL17B	NM_001352769.1		c.*21+2055C>G		intron	N/A	NP_001339698.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A	ENST00000320254.5	TSL:1 MANE Select	c.2338G>C	p.Val780Leu	missense	Exon 1 of 14	ENSP00000326324.5	A6NMS7
	LRRC37A	ENST00000393465.7	TSL:5	c.2338G>C	p.Val780Leu	missense	Exon 1 of 12	ENSP00000377108.2	A8MUI5
	LRRC37A	ENST00000496930.5	TSL:2	c.-277-2323G>C		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes AF: 0.0000773 AC: 9 AN: 116400 Hom.: 4 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00671

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00129 AC: 65 AN: 50466 AF XY: 0.000943

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0128

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000551

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000119 AC: 145 AN: 1220840 Hom.: 40 Cov.: 26 AF XY: 0.000110 AC XY: 68 AN XY: 615498

African (AFR) AF: 0.00 AC: 0 AN: 30166

American (AMR) AF: 0.00 AC: 0 AN: 36126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24474

East Asian (EAS) AF: 0.00543 AC: 139 AN: 25590

South Asian (SAS) AF: 0.00 AC: 0 AN: 79974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3720

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 922412

Other (OTH) AF: 0.0000972 AC: 5 AN: 51462

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000601 AC: 7 AN: 116486 Hom.: 3 Cov.: 18 AF XY: 0.0000725 AC XY: 4 AN XY: 55152

African (AFR) AF: 0.00 AC: 0 AN: 34402

American (AMR) AF: 0.00 AC: 0 AN: 10210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2968

East Asian (EAS) AF: 0.00522 AC: 7 AN: 1342

South Asian (SAS) AF: 0.00 AC: 0 AN: 3506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 55560

Other (OTH) AF: 0.00 AC: 0 AN: 1620

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.000102

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.4
DANN	Benign	0.81
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.20
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.039
Sift	Benign	0.13	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.27		Gain of sheet (P = 0.0827)
MVP		0.068
ClinPred		0.036	T
GERP RS		-4.1
Varity_R		0.079
gMVP		0.049
Mutation Taster		=100/0	polymorphism

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: rs557815137; hg19: chr17-44374837;