rs12118033

Positions:

• chr1-39092539-G-A

Variant summary

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

The ENST00000567887.5(MACF1):​c.220+8101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 152,136 control chromosomes in the GnomAD database, including 527 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 0.077 (527 hom., cov: 32)
• Consequence: MACF1 ENST00000567887.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93

Genes affected

MACF1 (HGNC:13664): (microtubule actin crosslinking factor 1) This gene encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. The encoded protein is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. Alternative splicing results in multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACF1	NM_012090.5	c.220+8101G>A		intron_variant			NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000361689.7	c.220+8101G>A		intron_variant		5		ENSP00000354573
MACF1	ENST00000372915.8	c.220+8101G>A		intron_variant		5		ENSP00000362006	P1
MACF1	ENST00000484793.5	c.220+8101G>A		intron_variant		2		ENSP00000434859

Frequencies

GnomAD3 genomes AF: 0.0770 AC: 11699 AN: 152018 Hom.: 523 Cov.: 32

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0386

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0934

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.0770 AC: 11721 AN: 152136 Hom.: 527 Cov.: 32 AF XY: 0.0783 AC XY: 5824 AN XY: 74358

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.0577

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0382

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.0934

Gnomad4 OTH AF: 0.0752

Alfa AF: 0.0858 Hom.: 344

Bravo AF: 0.0701

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs12118033; hg19: chr1-39558211;