5-62579802-C-T

Variant names:

• chr5-62579802-C-T
• rs771118373
• NM_181506.5:c.364C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_181506.5(LRRC70):​c.364C>T​(p.Arg122Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000505 in 1,543,994 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (1 hom.)
• Consequence: LRRC70 NM_181506.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.250
• Publications: 0 publications found

Genes affected

LRRC70 (HGNC:35155): (leucine rich repeat containing 70) Involved in positive regulation of response to cytokine stimulus. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

IPO11 (HGNC:20628): (importin 11) Importins, including IPO11, are a members of the karyopherin/importin-beta family of transport receptors (see KPNB1; 602738) that mediate nucleocytoplasmic transport of protein and RNA cargoes (Plafker and Macara, 2000 [PubMed 11032817]).[supplied by OMIM, Sep 2008]

IPO11-LRRC70 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050696105).
• BS2: High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181506.5. 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
	LRRC70	NM_181506.5	MANE Select	c.364C>T	p.Arg122Cys	missense	Exon 2 of 2	NP_852607.3
	IPO11	NM_016338.5	MANE Select	c.2583-11775C>T		intron	N/A	NP_057422.3
	IPO11	NM_001134779.2		c.2703-11775C>T		intron	N/A	NP_001128251.1	Q9UI26-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC70	ENST00000334994.6	TSL:1 MANE Select	c.364C>T	p.Arg122Cys	missense	Exon 2 of 2	ENSP00000399441.1	Q7Z2Q7
	IPO11	ENST00000325324.11	TSL:1 MANE Select	c.2583-11775C>T		intron	N/A	ENSP00000316651.6	Q9UI26-1
	IPO11	ENST00000424533.5	TSL:2	n.*73+319C>T		intron	N/A	ENSP00000395685.1	F8WDV0

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000864 AC: 13 AN: 150508 AF XY: 0.0000751

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000288

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000517

Gnomad OTH exome AF: 0.000473

GnomAD4 exome AF: 0.0000474 AC: 66 AN: 1391952 Hom.: 1 Cov.: 31 AF XY: 0.0000408 AC XY: 28 AN XY: 686732

African (AFR) AF: 0.0000320 AC: 1 AN: 31244

American (AMR) AF: 0.000369 AC: 13 AN: 35248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25050

East Asian (EAS) AF: 0.00 AC: 0 AN: 35642

South Asian (SAS) AF: 0.0000255 AC: 2 AN: 78324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49068

Middle Eastern (MID) AF: 0.000356 AC: 2 AN: 5620

European-Non Finnish (NFE) AF: 0.0000410 AC: 44 AN: 1074052

Other (OTH) AF: 0.0000693 AC: 4 AN: 57704

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152042 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74270

African (AFR) AF: 0.0000724 AC: 3 AN: 41416

American (AMR) AF: 0.000328 AC: 5 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000901 Hom.: 0

Bravo AF: 0.000136

ExAC AF: 0.0000484 AC: 1

ClinVar

ClinVar submissions

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	-0.30	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.84
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.98	L
PhyloP100		0.25
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.18
Sift	Benign	0.18	T
Sift4G	Uncertain	0.026	D
Polyphen		0.0050	B
Vest4		0.23
MVP		0.41
ClinPred		0.029	T
GERP RS		-1.3
Varity_R		0.072
gMVP		0.70
Mutation Taster		=97/3	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: rs771118373; hg19: chr5-61875629;