rs880226

Positions:

• chr6-25402075-A-G
• chr6-25402075-A-T

Variant summary

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

The NM_017640.6(CARMIL1):​c.139-18039A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 150,680 control chromosomes in the GnomAD database, including 15,101 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 0.44 (15101 hom., cov: 29)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444

Genes affected

CARMIL1 (HGNC:21581): (capping protein regulator and myosin 1 linker 1) Involved in several processes, including actin filament network formation; plasma membrane bounded cell projection organization; and positive regulation of cellular component organization. Located in several cellular components, including lamellipodium; macropinosome; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.139-18039A>G		intron_variant		ENST00000329474.7	NP_060110.4
LOC124901281	XR_007059512.1	n.991+18227T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.139-18039A>G		intron_variant		1	NM_017640.6	ENSP00000331983	P1
	ENST00000643807.1	n.230+18227T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.444 AC: 66835 AN: 150564 Hom.: 15082 Cov.: 29

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.444 AC: 66886 AN: 150680 Hom.: 15101 Cov.: 29 AF XY: 0.448 AC XY: 32915 AN XY: 73482

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.439

Alfa AF: 0.395 Hom.: 5866

Bravo AF: 0.442

Asia WGS AF: 0.389 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.14
DANN	Benign	0.81

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: rs880226; hg19: chr6-25402303;