rs10254391

Positions:

• chr7-156791873-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022458.4(LMBR1):​c.423+4516C>G variant causes a intron change. The variant allele was found at a frequency of 0.307 in 151,912 control chromosomes in the GnomAD database, including 7,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.31 (7465 hom., cov: 32)
• Consequence: LMBR1 NM_022458.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.35

Genes affected

LMBR1 (HGNC:13243): (limb development membrane protein 1) This gene encodes a member of the LMBR1-like membrane protein family. Another member of this protein family has been shown to be a lipocalin transmembrane receptor. A highly conserved, cis-acting regulatory module for the sonic hedgehog gene is located within an intron of this gene. Consequently, disruption of this genic region can alter sonic hedgehog expression and affect limb patterning, but it is not known if this gene functions directly in limb development. Mutations and chromosomal deletions and rearrangements in this genic region are associated with acheiropody and preaxial polydactyly, which likely result from altered sonic hedgehog expression. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 7-156791873-G-C is Benign according to our data. Variant chr7-156791873-G-C is described in ClinVar as [Benign]. Clinvar id is 768220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-156791873-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMBR1	NM_022458.4	c.423+4516C>G		intron_variant		ENST00000353442.10	NP_071903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBR1	ENST00000353442.10	c.423+4516C>G		intron_variant		1	NM_022458.4	ENSP00000326604	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46581 AN: 151792 Hom.: 7455 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46638 AN: 151912 Hom.: 7465 Cov.: 32 AF XY: 0.313 AC XY: 23219 AN XY: 74240

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.286

Alfa AF: 0.297 Hom.: 886

Bravo AF: 0.312

Asia WGS AF: 0.350 AC: 1219 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.68

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: rs10254391; hg19: chr7-156584567;