rs1239468440

Variant names:

• chr17-46512762-G-A
• rs1239468440
• NM_001006607.3:c.50G>A

Variant summary

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

The NM_001006607.3(LRRC37A2):​c.50G>A​(p.Arg17His) 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 10)
  • Exomes 𝑓: 0.00015 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A2 NM_001006607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0450
• Publications: 0 publications found

Genes affected

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17A (HGNC:24096): (ADP ribosylation factor like GTPase 17A) 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 (MetaRNN=0.05631712).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006607.3. 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
	LRRC37A2	NM_001006607.3	MANE Select	c.50G>A	p.Arg17His	missense	Exon 1 of 14	NP_001006608.2	A6NM11
	LRRC37A2	NM_001385803.1		c.50G>A	p.Arg17His	missense	Exon 1 of 14	NP_001372732.1
	ARL17A	NM_001288812.1		c.*22-3872C>T		intron	N/A	NP_001275741.1	Q8IVW1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A2	ENST00000576629.6	TSL:5 MANE Select	c.50G>A	p.Arg17His	missense	Exon 1 of 14	ENSP00000459551.1	A6NM11
	LRRC37A2	ENST00000706058.1		c.50G>A	p.Arg17His	missense	Exon 1 of 8	ENSP00000516210.1	A0A994J7J8
	LRRC37A2	ENST00000705813.1		c.-89+1154G>A		intron	N/A	ENSP00000516171.1	A0A994J7H6

Frequencies

GnomAD3 genomes AF: 0.000156 AC: 12 AN: 76764 Hom.: 0 Cov.: 10

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000248

Gnomad SAS AF: 0.000556

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000380

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000584 AC: 2 AN: 34268 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: 0.000201

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000153 AC: 90 AN: 587784 Hom.: 1 Cov.: 3 AF XY: 0.000180 AC XY: 53 AN XY: 293932

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

African (AFR) AF: 0.00 AC: 0 AN: 24736

American (AMR) AF: 0.00 AC: 0 AN: 31104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9470

East Asian (EAS) AF: 0.000261 AC: 9 AN: 34498

South Asian (SAS) AF: 0.000262 AC: 9 AN: 34348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33500

Middle Eastern (MID) AF: 0.00156 AC: 2 AN: 1286

European-Non Finnish (NFE) AF: 0.000171 AC: 67 AN: 392224

Other (OTH) AF: 0.000113 AC: 3 AN: 26618

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000156 AC: 12 AN: 76844 Hom.: 0 Cov.: 10 AF XY: 0.0000794 AC XY: 3 AN XY: 37798

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

African (AFR) AF: 0.00 AC: 0 AN: 28564

American (AMR) AF: 0.00 AC: 0 AN: 7652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1216

East Asian (EAS) AF: 0.000249 AC: 1 AN: 4016

South Asian (SAS) AF: 0.000559 AC: 1 AN: 1788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 78

European-Non Finnish (NFE) AF: 0.000380 AC: 10 AN: 26286

Other (OTH) AF: 0.00 AC: 0 AN: 866

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000811993), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000169 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

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	0.13
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.045
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.015
Sift	Benign	0.10	T
Sift4G	Benign	0.24	T
Polyphen		0.097	B
Vest4		0.18
MutPred		0.40		Gain of sheet (P = 0.0011)
MVP		0.014
ClinPred		0.055	T
GERP RS		-2.2
Varity_R		0.033
gMVP		0.071

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: rs1239468440; hg19: chr17-44590128;