rs74141216

Variant names:

• chr1-205448458-C-T
• rs74141216
• NM_001397426.2:c.-36-7396G>A

Variant summary

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

The NM_001397426.2(BLACAT1):​c.-36-7396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 524,714 control chromosomes in the GnomAD database, including 4,646 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 0.14 (1551 hom., cov: 31)
  • Exomes 𝑓: 0.12 (3095 hom.)
• Consequence: BLACAT1 NM_001397426.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

Genes affected

BLACAT1 (HGNC:48597): (BLACAT1 overlapping LEMD1 locus)

LEMD1 (HGNC:18725): (LEM domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MIR135B (HGNC:31760): (microRNA 135b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLACAT1	NM_001397426.2	c.-36-7396G>A		intron_variant	Intron 1 of 1	ENST00000629624.3	NP_001384355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLACAT1	ENST00000629624.3	c.-36-7396G>A		intron_variant	Intron 1 of 1	4	NM_001397426.2	ENSP00000498225.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21095 AN: 151952 Hom.: 1552 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0609

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.124 AC: 46050 AN: 372644 Hom.: 3095 AF XY: 0.125 AC XY: 26532 AN XY: 212664

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0977

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.0533

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.139 AC: 21114 AN: 152070 Hom.: 1551 Cov.: 31 AF XY: 0.140 AC XY: 10375 AN XY: 74344

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.0610

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.149

Alfa AF: 0.125 Hom.: 164

Bravo AF: 0.137

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs74141216; hg19: chr1-205417586;