chr17-46333520-T-C

Variant names:

• chr17-46333520-T-C
• rs273539
• NM_014834.4:c.4809+864T>C

Variant summary

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

The NM_014834.4(LRRC37A):​c.4809+864T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0098 (3 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

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.4809+864T>C		intron	N/A	NP_055649.4
	ARL17B	NM_001363805.1		c.526-2922A>G		intron	N/A	NP_001350734.1
	ARL17B	NM_001103154.2		c.259+19300A>G		intron	N/A	NP_001096624.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A	ENST00000320254.5	TSL:1 MANE Select	c.4809+864T>C		intron	N/A	ENSP00000326324.5
	ARL17B	ENST00000434041.6	TSL:1	c.259+19300A>G		intron	N/A	ENSP00000391751.2
	ARL17B	ENST00000572991.6	TSL:1	n.*93+3752A>G		intron	N/A	ENSP00000458681.2

Frequencies

GnomAD3 genomes AF: 0.00981 AC: 381 AN: 38846 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0131

Gnomad AMR AF: 0.00532

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000605

Gnomad SAS AF: 0.00155

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00178

Gnomad OTH AF: 0.00862

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00985 AC: 384 AN: 38988 Hom.: 3 Cov.: 0 AF XY: 0.00916 AC XY: 177 AN XY: 19332

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0132 AC: 348 AN: 26370

American (AMR) AF: 0.00529 AC: 26 AN: 4916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 302

East Asian (EAS) AF: 0.000605 AC: 2 AN: 3304

South Asian (SAS) AF: 0.00156 AC: 1 AN: 642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 36

European-Non Finnish (NFE) AF: 0.00178 AC: 3 AN: 1686

Other (OTH) AF: 0.00851 AC: 4 AN: 470

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.650 Hom.: 3585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.31
PhyloP100		-0.63
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: rs273539; hg19: chr17-44410886;