rs10243052

Variant names:

• chr7-156686464-A-G
• rs10243052
• NM_022458.4:c.1387+1566T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022458.4(LMBR1):​c.1387+1566T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 152,290 control chromosomes in the GnomAD database, including 645 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 0.077 (645 hom., cov: 33)
• Consequence: LMBR1 NM_022458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02
• Publications: 2 publications found

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]

LMBR1 Gene-Disease associations (from GenCC):

• polydactyly of a triphalangeal thumb

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• acheiropody

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• hypoplastic tibiae-postaxial polydactyly syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• laurin-Sandrow syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• syndactyly type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• triphalangeal thumb-polysyndactyly syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBR1	NM_022458.4	c.1387+1566T>C		intron_variant	Intron 16 of 16	ENST00000353442.10	NP_071903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBR1	ENST00000353442.10	c.1387+1566T>C		intron_variant	Intron 16 of 16	1	NM_022458.4	ENSP00000326604.7
LMBR1	ENST00000415428.5	c.1504+1566T>C		intron_variant	Intron 17 of 17	1		ENSP00000408256.1
LMBR1	ENST00000448926.5	n.*848-2301T>C		intron_variant	Intron 12 of 12	2		ENSP00000403052.1
LMBR1	ENST00000454132.5	n.*1424+1566T>C		intron_variant	Intron 18 of 18	2		ENSP00000414795.1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11667 AN: 152174 Hom.: 643 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0904

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0722

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

GnomAD4 genome AF: 0.0768 AC: 11698 AN: 152290 Hom.: 645 Cov.: 33 AF XY: 0.0775 AC XY: 5771 AN XY: 74464

African (AFR) AF: 0.148 AC: 6144 AN: 41542

American (AMR) AF: 0.0911 AC: 1394 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.151 AC: 781 AN: 5182

South Asian (SAS) AF: 0.0617 AC: 298 AN: 4826

European-Finnish (FIN) AF: 0.0444 AC: 472 AN: 10620

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0351 AC: 2388 AN: 68034

Other (OTH) AF: 0.0714 AC: 151 AN: 2114

Alfa AF: 0.0597 Hom.: 45

Bravo AF: 0.0841

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.7
DANN	Benign	0.82
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs10243052; hg19: chr7-156479158;