17-46297468-C-A

Variant names:

• chr17-46297468-C-A
• rs1275205266
• NM_014834.4:c.2335C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014834.4(LRRC37A):​c.2335C>A​(p.Arg779Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 0.0 (0 hom., cov: 18)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=0.255 with no splicing effect.

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.2335C>A	p.Arg779Arg	synonymous	Exon 1 of 14	NP_055649.4	A6NMS7
	ARL17B	NM_001103154.2		c.*21+2058G>T		intron	N/A	NP_001096624.1
	ARL17B	NM_001352769.1		c.*21+2058G>T		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.2335C>A	p.Arg779Arg	synonymous	Exon 1 of 14	ENSP00000326324.5	A6NMS7
	LRRC37A	ENST00000393465.7	TSL:5	c.2335C>A	p.Arg779Arg	synonymous	Exon 1 of 12	ENSP00000377108.2	A8MUI5
	LRRC37A	ENST00000496930.5	TSL:2	c.-277-2326C>A		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 117550 Hom.: 0 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: 0.00

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

GnomAD4 exome Cov.: 26

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 117638 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 55800

African (AFR) AF: 0.00 AC: 0 AN: 34734

American (AMR) AF: 0.00 AC: 0 AN: 10346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2990

East Asian (EAS) AF: 0.00 AC: 0 AN: 1416

South Asian (SAS) AF: 0.00 AC: 0 AN: 3560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 242

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 55916

Other (OTH) AF: 0.00 AC: 0 AN: 1638

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		0.26

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: rs1275205266; hg19: chr17-44374834;