rs750841606

Variant names:

• chr7-16527040-C-A
• rs750841606
• NM_001195280.2:c.88C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-16527040-C-A
• chr7-16527040-C-G
• chr7-16527040-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001195280.2(LRRC72):​c.88C>A​(p.Arg30Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC72 NM_001195280.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.00003192
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC72	NM_001195280.2	c.88C>A	p.Arg30Arg	splice_region_variant, synonymous_variant	Exon 1 of 9	ENST00000401542.3	NP_001182209.1
LRRC72	XM_011515057.2	c.88C>A	p.Arg30Arg	splice_region_variant, synonymous_variant	Exon 1 of 10		XP_011513359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC72	ENST00000401542.3	c.88C>A	p.Arg30Arg	splice_region_variant, synonymous_variant	Exon 1 of 9	5	NM_001195280.2	ENSP00000384971.2
LRRC72	ENST00000382124.7	n.88C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000371558.3
LRRC72	ENST00000482711.1	n.151C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 3	2
SOSTDC1	ENST00000396652.1	c.-320+3147G>T		intron_variant	Intron 1 of 4	2		ENSP00000379889.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1385388 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683660

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078750

Other (OTH) AF: 0.00 AC: 0 AN: 57908

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.53
DANN	Benign	0.67
PhyloP100		-1.0
PromoterAI		0.018	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0080
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: rs750841606; hg19: chr7-16566665;