rs7538300

Variant names:

• chr1-39187092-C-A
• rs7538300
• ENST00000567887.5:c.221-44090C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-39187092-C-A
• chr1-39187092-C-G
• chr1-39187092-C-T

Variant summary

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

The ENST00000567887.5(MACF1):​c.221-44090C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,106 control chromosomes in the GnomAD database, including 28,873 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 0.60 (28873 hom., cov: 29)
• Consequence: MACF1 ENST00000567887.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• Publications: 9 publications found

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]

MACF1 Gene-Disease associations (from GenCC):

• lissencephaly 9 with complex brainstem malformation

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics
• lissencephaly spectrum disorder with complex brainstem malformation

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACF1	NM_012090.5	c.221-44090C>A		intron_variant	Intron 1 of 92		NP_036222.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACF1	ENST00000567887.5	c.221-44090C>A		intron_variant	Intron 1 of 100	5		ENSP00000455823.1
MACF1	ENST00000372915.8	c.221-44090C>A		intron_variant	Intron 1 of 95	5		ENSP00000362006.4
MACF1	ENST00000361689.7	c.221-44090C>A		intron_variant	Intron 2 of 93	5		ENSP00000354573.2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90164 AN: 150990 Hom.: 28875 Cov.: 29

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.597 AC: 90157 AN: 151106 Hom.: 28873 Cov.: 29 AF XY: 0.604 AC XY: 44554 AN XY: 73796

African (AFR) AF: 0.334 AC: 13726 AN: 41062

American (AMR) AF: 0.671 AC: 10207 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2297 AN: 3466

East Asian (EAS) AF: 0.670 AC: 3423 AN: 5110

South Asian (SAS) AF: 0.771 AC: 3702 AN: 4802

European-Finnish (FIN) AF: 0.734 AC: 7588 AN: 10342

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.694 AC: 47052 AN: 67812

Other (OTH) AF: 0.611 AC: 1282 AN: 2098

Alfa AF: 0.662 Hom.: 91907

Bravo AF: 0.578

Asia WGS AF: 0.644 AC: 2239 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.71
PhyloP100		-0.50
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: rs7538300; hg19: chr1-39652764;