chr7-156681130-C-A

Variant names:

• chr7-156681130-C-A
• rs777769323
• NM_022458.4:c.*2948G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022458.4(LMBR1):​c.*2948G>T variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LMBR1 NM_022458.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.150
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMBR1	NM_022458.4	MANE Select	c.*2948G>T		3_prime_UTR	Exon 17 of 17	NP_071903.2
	LMBR1	NM_001350953.2		c.*2948G>T		3_prime_UTR	Exon 18 of 18	NP_001337882.1	Q8WVP7-3
	LMBR1	NM_001363409.2		c.*2948G>T		3_prime_UTR	Exon 17 of 17	NP_001350338.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMBR1	ENST00000353442.10	TSL:1 MANE Select	c.*2948G>T		3_prime_UTR	Exon 17 of 17	ENSP00000326604.7	Q8WVP7-1
	LMBR1	ENST00000931565.1		c.*2948G>T		3_prime_UTR	Exon 16 of 16	ENSP00000601624.1
	LMBR1	ENST00000875396.1		c.*2948G>T		3_prime_UTR	Exon 16 of 16	ENSP00000545455.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Polydactyly of a triphalangeal thumb (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.28
DANN	Benign	0.68
PhyloP100		0.15

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: rs777769323; hg19: chr7-156473824;