6-25607343-A-G

Position:

• chr6-25607343-A-G

Variant summary

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

The NM_017640.6(CARMIL1):​c.3847+1070A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,012 control chromosomes in the GnomAD database, including 6,386 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 0.29 (6386 hom., cov: 31)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

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 = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARMIL1	NM_017640.6	c.3847+1070A>G		intron_variant		ENST00000329474.7	NP_060110.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARMIL1	ENST00000329474.7	c.3847+1070A>G		intron_variant		1	NM_017640.6	ENSP00000331983.6
CARMIL1	ENST00000700669.1	c.3829+1070A>G		intron_variant				ENSP00000515137.1
CARMIL1	ENST00000635618.1	n.2647+1070A>G		intron_variant		5		ENSP00000489114.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43759 AN: 151894 Hom.: 6375 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.288 AC: 43799 AN: 152012 Hom.: 6386 Cov.: 31 AF XY: 0.284 AC XY: 21069 AN XY: 74300

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.281

Alfa AF: 0.297 Hom.: 9430

Bravo AF: 0.293

Asia WGS AF: 0.347 AC: 1205 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	0.52
DANN	Benign	0.73

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: rs742132; hg19: chr6-25607571;