chr6-25488355-C-T

Variant names:

• chr6-25488355-C-T
• rs2274089
• NM_017640.6:c.962-127C>T

Variant summary

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

The NM_017640.6(CARMIL1):​c.962-127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 748,486 control chromosomes in the GnomAD database, including 2,179 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 0.059 (337 hom., cov: 32)
  • Exomes 𝑓: 0.070 (1842 hom.)
• Consequence: CARMIL1 NM_017640.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 23 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017640.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL1	NM_017640.6	MANE Select	c.962-127C>T		intron	N/A	NP_060110.4
	CARMIL1	NM_001173977.2		c.962-127C>T		intron	N/A	NP_001167448.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL1	ENST00000329474.7	TSL:1 MANE Select	c.962-127C>T		intron	N/A	ENSP00000331983.6
	CARMIL1	ENST00000700669.1		c.962-127C>T		intron	N/A	ENSP00000515137.1

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8944 AN: 152142 Hom.: 336 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0882

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0700 AC: 41740 AN: 596226 Hom.: 1842 AF XY: 0.0673 AC XY: 21591 AN XY: 320658

African (AFR) AF: 0.0155 AC: 261 AN: 16804

American (AMR) AF: 0.0591 AC: 2197 AN: 37168

Ashkenazi Jewish (ASJ) AF: 0.0226 AC: 419 AN: 18502

East Asian (EAS) AF: 0.0344 AC: 1210 AN: 35156

South Asian (SAS) AF: 0.0225 AC: 1410 AN: 62646

European-Finnish (FIN) AF: 0.0911 AC: 3994 AN: 43824

Middle Eastern (MID) AF: 0.0304 AC: 121 AN: 3980

European-Non Finnish (NFE) AF: 0.0866 AC: 29994 AN: 346396

Other (OTH) AF: 0.0672 AC: 2134 AN: 31750

GnomAD4 genome AF: 0.0587 AC: 8945 AN: 152260 Hom.: 337 Cov.: 32 AF XY: 0.0578 AC XY: 4304 AN XY: 74434

African (AFR) AF: 0.0156 AC: 648 AN: 41582

American (AMR) AF: 0.0543 AC: 831 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.0276 AC: 143 AN: 5182

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4820

European-Finnish (FIN) AF: 0.0947 AC: 1004 AN: 10606

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0882 AC: 5995 AN: 67992

Other (OTH) AF: 0.0559 AC: 118 AN: 2110

Alfa AF: 0.0725 Hom.: 1263

Bravo AF: 0.0536

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.36
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: rs2274089; hg19: chr6-25488583;