11-68918811-C-G

Position:

• chr11-68918811-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002180.3(IGHMBP2):​c.1060+928C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,132 control chromosomes in the GnomAD database, including 44,546 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 0.76 (44546 hom., cov: 32)
• Consequence: IGHMBP2 NM_002180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

IGHMBP2 (HGNC:5542): (immunoglobulin mu DNA binding protein 2) This gene encodes a helicase superfamily member that binds a specific DNA sequence from the immunoglobulin mu chain switch region. Mutations in this gene lead to spinal muscle atrophy with respiratory distress type 1. [provided by RefSeq, Jul 2008]

IGHMBP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGHMBP2	NM_002180.3	c.1060+928C>G		intron_variant		ENST00000255078.8	NP_002171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGHMBP2	ENST00000255078.8	c.1060+928C>G		intron_variant		1	NM_002180.3	ENSP00000255078.4

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114983 AN: 152014 Hom.: 44517 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.756 AC: 115063 AN: 152132 Hom.: 44546 Cov.: 32 AF XY: 0.755 AC XY: 56156 AN XY: 74358

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.784

Alfa AF: 0.750 Hom.: 2682

Bravo AF: 0.755

Asia WGS AF: 0.620 AC: 2157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.44
DANN	Benign	0.58

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: rs654797; hg19: chr11-68686279;