7-16567471-G-A

Variant names:

• chr7-16567471-G-A
• rs201481861
• NM_001195280.2:c.598G>A

Variant summary

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

The NM_001195280.2(LRRC72):​c.598G>A​(p.Gly200Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,532,474 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000099 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: LRRC72 NM_001195280.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.109
• Publications: 0 publications found

Genes affected

LRRC72 (HGNC:42972): (leucine rich repeat containing 72)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.033952773).
• BP6: Variant 7-16567471-G-A is Benign according to our data. Variant chr7-16567471-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2352014.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC72	NM_001195280.2	c.598G>A	p.Gly200Arg	missense_variant	Exon 7 of 9	ENST00000401542.3	NP_001182209.1
LRRC72	XM_011515057.2	c.598G>A	p.Gly200Arg	missense_variant	Exon 7 of 10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3	c.598G>A	p.Gly200Arg	missense_variant	Exon 7 of 9	5	NM_001195280.2	ENSP00000384971.2

Frequencies

GnomAD3 genomes AF: 0.0000995 AC: 15 AN: 150808 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

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: 0.000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000626 AC: 9 AN: 143710 AF XY: 0.0000771

Gnomad AFR exome AF: 0.000153

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: 0.000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000193 AC: 267 AN: 1381554 Hom.: 0 Cov.: 31 AF XY: 0.000188 AC XY: 128 AN XY: 681110

African (AFR) AF: 0.000161 AC: 5 AN: 31132

American (AMR) AF: 0.000175 AC: 6 AN: 34358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24680

East Asian (EAS) AF: 0.0000283 AC: 1 AN: 35362

South Asian (SAS) AF: 0.0000132 AC: 1 AN: 75736

European-Finnish (FIN) AF: 0.0000421 AC: 2 AN: 47516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.000225 AC: 241 AN: 1069972

Other (OTH) AF: 0.000192 AC: 11 AN: 57198

GnomAD4 genome AF: 0.0000994 AC: 15 AN: 150920 Hom.: 0 Cov.: 30 AF XY: 0.0000679 AC XY: 5 AN XY: 73640

African (AFR) AF: 0.0000974 AC: 4 AN: 41086

American (AMR) AF: 0.0000659 AC: 1 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000148 AC: 10 AN: 67766

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.0000559 Hom.: 0

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.000105 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 14, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.67
DANN	Benign	0.28
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.94	L
PhyloP100		-0.11
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.093
Sift	Benign	0.30	T
Sift4G	Benign	0.86	T
Vest4		0.11
MutPred		0.58		Gain of MoRF binding (P = 0.0134);
MVP		0.17
ClinPred		0.096	T
GERP RS		-9.6
Varity_R		0.14
gMVP		0.21
Mutation Taster		=98/2	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: rs201481861; hg19: chr7-16607096;