7-98315625-A-ATAAG

Variant names:

• chr7-98315625-A-ATAAG
• rs372695844
• NM_018842.5:c.487-14_487-13insCTTA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018842.5(BAIAP2L1):​c.487-14_487-13insCTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 982,080 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: BAIAP2L1 NM_018842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

Genes affected

BAIAP2L1 (HGNC:21649): (BAR/IMD domain containing adaptor protein 2 like 1) This gene encodes a member of the IMD (IRSp53/MIM homology domain) family. Members of this family can be subdivided in two groups, the IRSp53-like and MIM-like, based on the presence or absence of the SH3 (Src homology 3) domain. The protein encoded by this gene contains a conserved IMD, also known as F-actin bundling domain, at the N-terminus, and a canonical SH3 domain near the C-terminus, so it belongs to the IRSp53-like group. This protein is the substrate for insulin receptor tyrosine kinase and binds to the small GTPase Rac. It is involved in signal transduction pathways that link deformation of the plasma membrane and remodeling of the actin cytoskeleton. It also promotes actin assembly and membrane protrusions when overexpressed in mammalian cells, and is essential to the formation of a potent actin assembly complex during EHEC (Enterohemorrhagic Escherichia coli) pedestal formation. [provided by RefSeq, Oct 2009]

BRI3 (HGNC:1109): (brain protein I3) Enables identical protein binding activity. Predicted to be located in azurophil granule membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAIAP2L1	NM_018842.5	c.487-14_487-13insCTTA		intron_variant	Intron 6 of 13	ENST00000005260.9	NP_061330.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAIAP2L1	ENST00000005260.9	c.487-14_487-13insCTTA		intron_variant	Intron 6 of 13	1	NM_018842.5	ENSP00000005260.8
BAIAP2L1	ENST00000462558.5	n.703-14_703-13insCTTA		intron_variant	Intron 6 of 9	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 982080 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 481200

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19944

American (AMR) AF: 0.00 AC: 0 AN: 15792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15264

East Asian (EAS) AF: 0.00 AC: 0 AN: 26770

South Asian (SAS) AF: 0.00 AC: 0 AN: 31972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2930

European-Non Finnish (NFE) AF: 0.00000126 AC: 1 AN: 794302

Other (OTH) AF: 0.00 AC: 0 AN: 39684

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs372695844; hg19: chr7-97944937;