rs4798680

Variant names:

• chr18-8730728-G-A
• rs4798680
• NM_001395333.1:c.1437+10232G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-8730728-G-A
• chr18-8730728-G-C

Variant summary

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

The NM_001395333.1(MTCL1):​c.1437+10232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,038 control chromosomes in the GnomAD database, including 9,093 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 0.33 (9093 hom., cov: 32)
• Consequence: MTCL1 NM_001395333.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 2 publications found

Genes affected

MTCL1 (HGNC:29121): (microtubule crosslinking factor 1) Enables microtubule binding activity. Predicted to be involved in establishment or maintenance of epithelial cell apical/basal polarity; microtubule bundle formation; and positive regulation of protein targeting to membrane. Located in midbody and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCL1	NM_001395333.1	c.1437+10232G>A		intron_variant	Intron 3 of 14	ENST00000695636.1	NP_001382262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTCL1	ENST00000695636.1	c.1437+10232G>A		intron_variant	Intron 3 of 14		NM_001395333.1	ENSP00000512073.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49703 AN: 151920 Hom.: 9087 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.351

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 49716 AN: 152038 Hom.: 9093 Cov.: 32 AF XY: 0.329 AC XY: 24453 AN XY: 74322

African (AFR) AF: 0.173 AC: 7185 AN: 41498

American (AMR) AF: 0.279 AC: 4266 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3466

East Asian (EAS) AF: 0.573 AC: 2956 AN: 5160

South Asian (SAS) AF: 0.473 AC: 2278 AN: 4812

European-Finnish (FIN) AF: 0.349 AC: 3692 AN: 10578

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26849 AN: 67952

Other (OTH) AF: 0.357 AC: 748 AN: 2098

Alfa AF: 0.332 Hom.: 1316

Bravo AF: 0.314

Asia WGS AF: 0.494 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4798680; hg19: chr18-8730726;