NM_022458.4:c.1387+1607T>C

Variant names:

• chr7-156686423-A-G
• rs10242938
• NM_022458.4:c.1387+1607T>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+1607T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,250 control chromosomes in the GnomAD database, including 618 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 0.075 (618 hom., cov: 33)
• Consequence: LMBR1 NM_022458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBR1	NM_022458.4	c.1387+1607T>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+1607T>C		intron_variant	Intron 16 of 16	1	NM_022458.4	ENSP00000326604.7
LMBR1	ENST00000415428.5	c.1504+1607T>C		intron_variant	Intron 17 of 17	1		ENSP00000408256.1
LMBR1	ENST00000448926.5	n.*848-2260T>C		intron_variant	Intron 12 of 12	2		ENSP00000403052.1
LMBR1	ENST00000454132.5	n.*1424+1607T>C		intron_variant	Intron 18 of 18	2		ENSP00000414795.1

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11456 AN: 152132 Hom.: 616 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0754 AC: 11484 AN: 152250 Hom.: 618 Cov.: 33 AF XY: 0.0763 AC XY: 5681 AN XY: 74450

African (AFR) AF: 0.143 AC: 5947 AN: 41524

American (AMR) AF: 0.0902 AC: 1380 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.151 AC: 783 AN: 5180

South Asian (SAS) AF: 0.0619 AC: 298 AN: 4816

European-Finnish (FIN) AF: 0.0445 AC: 472 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0351 AC: 2387 AN: 68030

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.0414 Hom.: 48

Bravo AF: 0.0822

Asia WGS AF: 0.0940 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.88
PhyloP100		0.50
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: rs10242938; hg19: chr7-156479117;