rs74141216

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000629624.3(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 ENST00000629624.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000629624.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLACAT1	NM_001397426.2	MANE Select	c.-36-7396G>A		intron	N/A	NP_001384355.1
	MIR135B	NR_029893.1		n.-60G>A		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLACAT1	ENST00000629624.3	TSL:4 MANE Select	c.-36-7396G>A		intron	N/A	ENSP00000498225.1
	LEMD1	ENST00000367154.5	TSL:2	c.-39+1410G>A		intron	N/A	ENSP00000356122.1
	LEMD1	ENST00000495594.2	TSL:3	c.-39+7459G>A		intron	N/A	ENSP00000479306.1

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

African (AFR) AF: 0.188 AC: 1927 AN: 10262

American (AMR) AF: 0.0977 AC: 3431 AN: 35126

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 2371 AN: 11550

East Asian (EAS) AF: 0.0533 AC: 692 AN: 12990

South Asian (SAS) AF: 0.129 AC: 8524 AN: 65980

European-Finnish (FIN) AF: 0.152 AC: 4516 AN: 29672

Middle Eastern (MID) AF: 0.178 AC: 281 AN: 1576

European-Non Finnish (NFE) AF: 0.117 AC: 22192 AN: 189178

Other (OTH) AF: 0.130 AC: 2116 AN: 16310

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

African (AFR) AF: 0.188 AC: 7799 AN: 41462

American (AMR) AF: 0.112 AC: 1717 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3464

East Asian (EAS) AF: 0.0610 AC: 316 AN: 5180

South Asian (SAS) AF: 0.121 AC: 585 AN: 4818

European-Finnish (FIN) AF: 0.159 AC: 1683 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7919 AN: 67966

Other (OTH) AF: 0.149 AC: 313 AN: 2096

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		1.8
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: rs74141216; hg19: chr1-205417586;