7-98315625-A-ATAATAAT

Variant names:

• chr7-98315625-A-ATAATAAT
• rs372695844
• NM_018842.5:c.487-14_487-13insATTATTA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018842.5(BAIAP2L1):​c.487-14_487-13insATTATTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 149,162 control chromosomes in the GnomAD database, including 68 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.026 (68 hom., cov: 32)
  • Exomes 𝑓: 0.026 (1108 hom.)
  • Failed GnomAD Quality Control
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0261 (3889/149162) while in subpopulation NFE AF = 0.0382 (2574/67448). AF 95% confidence interval is 0.0369. There are 68 homozygotes in GnomAd4. There are 1894 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 68 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3892 AN: 149088 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.00856

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.0345

Gnomad EAS AF: 0.00272

Gnomad SAS AF: 0.0231

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0387

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.0313

GnomAD2 exomes AF: 0.0203 AC: 1556 AN: 76812 AF XY: 0.0204

Gnomad AFR exome AF: 0.00217

Gnomad AMR exome AF: 0.00921

Gnomad ASJ exome AF: 0.0183

Gnomad EAS exome AF: 0.000948

Gnomad FIN exome AF: 0.0293

Gnomad NFE exome AF: 0.0238

Gnomad OTH exome AF: 0.0227

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0258 AC: 25244 AN: 979612 Hom.: 1108 Cov.: 14 AF XY: 0.0261 AC XY: 12541 AN XY: 480018

African (AFR) AF: 0.00532 AC: 106 AN: 19930

American (AMR) AF: 0.0130 AC: 205 AN: 15776

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 334 AN: 15230

East Asian (EAS) AF: 0.000934 AC: 25 AN: 26764

South Asian (SAS) AF: 0.0180 AC: 573 AN: 31912

European-Finnish (FIN) AF: 0.0314 AC: 1109 AN: 35354

Middle Eastern (MID) AF: 0.0321 AC: 94 AN: 2924

European-Non Finnish (NFE) AF: 0.0276 AC: 21875 AN: 792124

Other (OTH) AF: 0.0233 AC: 923 AN: 39598

GnomAD4 genome AF: 0.0261 AC: 3889 AN: 149162 Hom.: 68 Cov.: 32 AF XY: 0.0260 AC XY: 1894 AN XY: 72860

African (AFR) AF: 0.00854 AC: 346 AN: 40518

American (AMR) AF: 0.0203 AC: 305 AN: 15008

Ashkenazi Jewish (ASJ) AF: 0.0345 AC: 119 AN: 3454

East Asian (EAS) AF: 0.00272 AC: 14 AN: 5138

South Asian (SAS) AF: 0.0232 AC: 111 AN: 4794

European-Finnish (FIN) AF: 0.0343 AC: 327 AN: 9542

Middle Eastern (MID) AF: 0.0352 AC: 10 AN: 284

European-Non Finnish (NFE) AF: 0.0382 AC: 2574 AN: 67448

Other (OTH) AF: 0.0310 AC: 64 AN: 2066

Alfa AF: 0.00896 Hom.: 293

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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;