7-150331083-A-G

Variant names:

• chr7-150331083-A-G
• rs754425171
• NM_001142928.2:c.-145+5073A>G

Variant summary

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

The NM_001142928.2(LRRC61):​c.-145+5073A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,394 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (1 hom.)
• Consequence: LRRC61 NM_001142928.2 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.361
• Publications: 0 publications found

Genes affected

LRRC61 (HGNC:21704): (leucine rich repeat containing 61) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293476 (HGNC:):

ZBED10P (HGNC:21720): (zinc finger BED-type containing 10, pseudogene)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034951687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC61	NM_001142928.2	c.-145+5073A>G		intron_variant	Intron 2 of 2	ENST00000359623.9	NP_001136400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC61	ENST00000359623.9	c.-145+5073A>G		intron_variant	Intron 2 of 2	2	NM_001142928.2	ENSP00000352642.4

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152120 Hom.: 0 Cov.: 32

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: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 249676 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000370 AC: 54 AN: 1461274 Hom.: 1 Cov.: 31 AF XY: 0.0000399 AC XY: 29 AN XY: 726966

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111900

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68002

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.0000337 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.679A>G (p.I227V) alteration is located in exon 1 (coding exon 1) of the ZBED6CL gene. This alteration results from a A to G substitution at nucleotide position 679, causing the isoleucine (I) at amino acid position 227 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.9
DANN	Benign	0.67
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.36
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.035
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.040
MutPred		0.15		Gain of sheet (P = 0.1208);
MVP		0.014
MPC		0.054
ClinPred		0.046	T
GERP RS		1.8
Varity_R		0.058
gMVP		0.065

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: rs754425171; hg19: chr7-150028172; COSMIC: COSV59604973; COSMIC: COSV59604973;