chr1-39369868-T-C

Variant names:

• chr1-39369868-T-C
• rs582883
• NM_001394062.1:c.12939-162T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394062.1(MACF1):​c.12939-162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,076 control chromosomes in the GnomAD database, including 11,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (11150 hom., cov: 32)
• Consequence: MACF1 NM_001394062.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.232
• Publications: 10 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), Ambry Genetics, Orphanet
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-39369868-T-C is Benign according to our data. Variant chr1-39369868-T-C is described in ClinVar as Benign. ClinVar VariationId is 1257453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394062.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACF1	NM_001394062.1	MANE Select	c.12939-162T>C		intron	N/A	NP_001380991.1	H3BPE1
	MACF1	NM_012090.5		c.6753-162T>C		intron	N/A	NP_036222.3	Q9UPN3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACF1	ENST00000564288.6	TSL:5 MANE Select	c.12939-162T>C		intron	N/A	ENSP00000455274.1	H3BPE1
	MACF1	ENST00000567887.5	TSL:5	c.13050-162T>C		intron	N/A	ENSP00000455823.1	H3BQK9
	MACF1	ENST00000372915.8	TSL:5	c.12954-162T>C		intron	N/A	ENSP00000362006.4	A0A7P0MQR8

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55448 AN: 151958 Hom.: 11116 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.365 AC: 55532 AN: 152076 Hom.: 11150 Cov.: 32 AF XY: 0.359 AC XY: 26710 AN XY: 74354

African (AFR) AF: 0.541 AC: 22454 AN: 41470

American (AMR) AF: 0.308 AC: 4711 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2147 AN: 5160

South Asian (SAS) AF: 0.220 AC: 1062 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2745 AN: 10584

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20344 AN: 67984

Other (OTH) AF: 0.358 AC: 754 AN: 2108

Alfa AF: 0.310 Hom.: 4594

Bravo AF: 0.379

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.27
PhyloP100		-0.23
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: rs582883; hg19: chr1-39835540;