chr7-16530199-G-C

Position:

• chr7-16530199-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195280.2(LRRC72):​c.91-2296G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 152,200 control chromosomes in the GnomAD database, including 86 homozygotes. 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 0.023 (86 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC72 NM_001195280.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

Genes affected

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

SOSTDC1 (HGNC:21748): (sclerostin domain containing 1) This gene is a member of the sclerostin family and encodes an N-glycosylated, secreted protein with a C-terminal cystine knot-like domain. This protein functions as a bone morphogenetic protein (BMP) antagonist. Specifically, it directly associates with BMPs, prohibiting them from binding their receptors, thereby regulating BMP signaling during cellular proliferation, differentiation, and programmed cell death. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC72	NM_001195280.2	c.91-2296G>C		intron_variant		ENST00000401542.3	NP_001182209.1
LRRC72	XM_011515057.2	c.91-2296G>C		intron_variant			XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3	c.91-2296G>C		intron_variant		5	NM_001195280.2	ENSP00000384971	P1
SOSTDC1	ENST00000396652.1	c.-332C>G		5_prime_UTR_variant	1/5	2		ENSP00000379889
LRRC72	ENST00000382124.7	c.91-2296G>C		intron_variant, NMD_transcript_variant		3		ENSP00000371558
LRRC72	ENST00000482711.1	n.154-2296G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3416 AN: 152082 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0301

Gnomad FIN AF: 0.00595

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00739

Gnomad OTH AF: 0.0177

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0225 AC: 3428 AN: 152200 Hom.: 86 Cov.: 32 AF XY: 0.0229 AC XY: 1705 AN XY: 74422

Gnomad4 AFR AF: 0.0598

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0301

Gnomad4 FIN AF: 0.00595

Gnomad4 NFE AF: 0.00740

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0197 Hom.: 12

Bravo AF: 0.0232

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs35324397; hg19: chr7-16569824;