11-68932891-C-T

Variant summary

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

The NM_002180.3(IGHMBP2):c.1236-408C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 231,170 control chromosomes in the GnomAD database, including 69,293 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 (44629 hom., cov: 30)
  • Exomes 𝑓: 0.78 (24664 hom.)
• Consequence: IGHMBP2 NM_002180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• 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	UniProt
IGHMBP2	NM_002180.3	c.1236-408C>T		intron_variant		ENST00000255078.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGHMBP2	ENST00000255078.8	c.1236-408C>T		intron_variant		1	NM_002180.3	P1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115071 AN: 151886 Hom.: 44599 Cov.: 30

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.485

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

GnomAD4 exome AF: 0.781 AC: 61836 AN: 79166 Hom.: 24664 Cov.: 0 AF XY: 0.780 AC XY: 32054 AN XY: 41118

Gnomad4 AFR exome AF: 0.611

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.810

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.732

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.771

GnomAD4 genome AF: 0.758 AC: 115152 AN: 152004 Hom.: 44629 Cov.: 30 AF XY: 0.757 AC XY: 56200 AN XY: 74284

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.728

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.783

Alfa AF: 0.814 Hom.: 26260

Bravo AF: 0.757

Asia WGS AF: 0.620 AC: 2158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.14
Dann	Benign	0.55

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: rs655915; hg19: chr11-68700359;